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Strategies aimed at expediting immunisation campaigns against COVID-19 include providing single vaccine doses to individuals with previous exposure to SARS-CoV-2 and delaying second doses. While such approaches are effective at the population level, immunogenicity yielded by one dose of vaccines in immunocompromised patients may be alarmingly low.1 2 Biological (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) interfere with the immune system at multiple levels and may variably reduce response to viral vaccines.3 Limited data on small numbers of rheumatic patients with variable diagnoses and treatments hamper definitive conclusions on the possible impact of immune-mediated inflammatory diseases, immunomodulatory drugs or both on the efficacy of the new generation of mRNA vaccines.4 5 Here we present interim data analysis on the immunogenicity of the BNT162b2 COVID-19 vaccine in 140 patients with chronic inflammatory arthritis all treated with b/tsDMARDs at the Division of Rheumatology of the IRCCS Policlinico San Matteo University Hospital of Pavia, receiving the first dose of vaccine between 24 and 31 March 2021. Patients were advised to discontinue both the b/tsDMARD and concomitant methotrexate around vaccination. In particular, the following suggestions were made: (1) for all the bDMARDs and methotrexate, withholding of therapy in the 7 days before and after vaccination; and (2) for tsDMARDs, withholding of therapy from the day before until day 7 after vaccination. For glucocorticoids and conventional synthetic DMARDs other than methotrexate, no modifications were advised. Blood samples were obtained immediately before vaccination and at day 21 after the first dose. Serum samples were tested using chemiluminescent immunoassay (LIAISON SARS-CoV-2 S1/S2 IgG; DiaSorin) for the quantitative characterisation of SARS-CoV-2 anti-S1 and anti-S2 IgG antibodies, with values >15 AU/mL indicating a positive result. Demographic and clinical variables were retrieved from the last available rheumatological assessment (median (IQR) 14 (5–19) days before vaccination) …

The objective of this study is to describe the possible prognostic impact of smoking habit on adult-onset Still’s disease (AOSD) patients, by the assessment of clinical characteristics, life-threatening complications occurrence, and mortality in smokers than non-smokers. A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was conducted. Out of 185 AOSD assessed patients, 45 smokers were identified. These showed a higher frequency of pericarditis (35.5% vs 16.4%, p = 0.011), pleuritis (33.3% vs 14.3%, p = 0.008), and abdominal pain (17.7% vs 6.4%, p = 0.035). Furthermore, smokers showed higher values of systemic score (6.4 ± 2.2 vs 5.4 ± 1.8, p = 0.004), an increased rate of macrophage activation syndrome (MAS) (28.9% vs 6.4%, p < 0.0001) and of parenchymal lung disease (17.7% vs 12.6%, p = 0.035). Although not significant, these patients more frequently experienced a poor prognosis (13.3% vs 4.3%, p = 0.074). Smoking habit predicted MAS occurrence in both univariate (HR: 5.98, 95% CI: 2.45–14.57, p < 0.0001) and multivariate regression models (HR: 6.21, 95% CI: 2.46–15.70, p < 0.0001). Smokers had a significant higher risk of parenchymal lung disease in both univariate (HR: 3.97, 95% CI: 1.43–11.02, p = 0.008) and multivariate regression models (HR: 3.90, 95% CI: 1.36–11.23, p = 0.012). Smoking habit also increased the risk of mortality in univariate regression model (HR: 4.25, 95% CI: 1.33–13.55, p = 0.015). Smoking habit resulted to be a negative prognostic factor on AOSD patients. Smokers were characterised by a higher frequency of serositis and higher values of systemic score. Additionally, these patients were more frequently burdened by MAS and parenchymal lung disease associated with a poor prognosis.Key points•Smoking habit resulted to be a negative prognostic factor on AOSD.•Smokers were characterised by an increased frequency of serositis and higher values of systemic score.•Cigarette exposure was associated with MAS and parenchymal lung disease in AOSD.

EULAR recommendations do not suggest which biologic disease-modifying anti-rheumatic drug (bDMARD) should be preferred after failure of a first bDMARD in the treatment of rheumatoid arthritis (RA). In particular, few data are available regarding the effectiveness of a second-line bDMARD after failure of abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX). The aim of this study was to analyze the retention rate of a second line with tumor necrosis factor inhibitors (TNFi) or other mechanisms of action (MoAs), after the failure of either RTX, TCZ, or ABA.Two hundred and seventy-eight RA patients from the Italian GISEA registry were included in the study. RTX was the first bDMARD in 18% of patients, ABA in 45.7%, and TCZ in 36.3%, while the second bDMARD was a TNFi (group 1) in 129 patients and an agent with a different MoA (group 2) in 149.During a median follow-up of 22 months (IQR 68), 129 patients discontinued their treatment; patients of group 1 discontinued the treatment more frequently than patients of group 2 (p0.001) with retention rates of 33.6±5.7% and 63.6±4.6% after 104 weeks for group 1 and group 2, respectively (p0.001). At multivariate analysis, the mechanism of action was the only predictor for the maintenance in therapy.According to our data, ABA, RTX, and TCZ seem to maintain a good retention rate also when used as a second-line therapy, suggesting their use after the failure of a non-TNFi as first-line therapy. However, specifically designed studies are needed to evaluate the more appropriate therapeutic strategies in RA, according to the first-line drug, including new targeted synthetic DMARDs. Key Points • A large proportion of rheumatoid arthritis patients fail the first biologic DMARD. • Few data are available about the efficacy of biologic DMARD after the failure of a non-TNF inhibitor. • Abatacept, rituximab, or tocilizumab seem to maintain a good retention rate after the failure of a first-course therapy with a non-TNF inhibitor.

BackgroundPrevalence and outcomes of coronavirus disease (COVID)-19 in relation to immunomodulatory medications are still unknown. The aim of the study is to investigate the impact of glucocorticoids and immunosuppressive agents on COVID-19 in a large cohort of patients with chronic immune-mediated inflammatory arthritis.MethodsThe study was conducted in the arthritis outpatient clinic at two large academic hospitals in the COVID-19 most endemic area of Northern Italy (Lombardy). We circulated a cross-sectional survey exploring the prevalence of severe acute respiratory syndrome-coronavirus-2 nasopharyngeal swab positivity and the occurrence of acute respiratory illness (fever and/or cough and/or dyspnea), administered face-to-face or by phone to consecutive patients from 25 February to 20 April 2020. COVID-19 cases were defined as confirmed or highly suspicious according to the World Health Organization criteria. The impact of medications on COVID-19 development was evaluated.ResultsThe study population included 2050 adults with chronic inflammatory arthritis receiving glucocorticoids, conventional-synthetic (cs), or targeted-synthetic/biological (ts/b) disease-modifying drugs (DMARDs). Laboratory-confirmed COVID-19 and highly suspicious infection were recorded in 1.1% and 1.4% of the population, respectively. Treatment with glucocorticoids was independently associated with increased risk of COVID-19 (adjusted OR [95% CI] ranging from 1.23 [1.04–1.44] to 3.20 [1.97–5.18] depending on the definition used). Conversely, patients treated with ts/bDMARDs were at reduced risk (adjusted OR ranging from 0.46 [0.18–1.21] to 0.47 [0.46–0.48]). No independent effects of csDMARDs, age, sex, and comorbidities were observed.ConclusionsDuring the COVID-19 outbreak, treatment with immunomodulatory medications appears safe. Conversely, glucocorticoids, even at low-dose, may confer increased risk of infection.Trial registrationRetrospectively registered. Not applicable.

Objective To describe the incidence and severity of coronavirus disease 2019 (COVID-19) in patients with rheumatic diseases treated with targeted synthetic or biologic disease-modifying antirheumatic drugs (DMARDs) compared with that in the general population living in the same Italian region. Methods Patients followed up at 2 rheumatology referral centers in Lombardy from February 25, 2020 to April 10, 2020 were invited to participate in a survey designed to identify patients who had confirmed COVID-19, close contact with others with confirmed COVID-19, or symptoms of the infection, and to detect changes in work, behavior, and disease management made in an attempt to prevent infection. The incidence of COVID-19 in the Lombardy population was obtained from the National Institute of Statistics. COVID-19 cases were confirmed by nasopharyngeal swab. Results The survey was given to 955 patients (531 patients with rheumatoid arthritis, 203 patients with psoriatic arthritis, 181 patients with spondyloarthritis, and 40 patients with connective tissue diseases, vasculitides, or autoinflammatory diseases). These patients had a mean age of 53.7 years, and 67.4% were women. The rate of response to the survey was 98.05%, and the incidence of confirmed COVID-19 cases was consistent with that in the general population (0.62% versus 0.66%; P = 0.92). None of the patients had severe complications or required intensive care treatment, and all of the patients who tested positive for COVID-19 temporarily discontinued ongoing targeted synthetic drug or biologic DMARD therapy. Almost all patients took precautions to prevent the COVID-19 infection (90.6%), and almost all continued treatment with targeted synthetic drugs or biologic DMARDs (93.2%). Disease activity remained stable in 89.5% of patients. Conclusion Our results reflected the attitude of patients with rheumatic diseases regarding the prevention of the infection while maintaining their long-term treatment regimens. The incidence and severity of COVID-19 in patients treated with targeted synthetic drugs or biologic DMARDs was not significantly different from that in the general population in the same region.

Background:Schnitzler’s syndrome is an autoinflammatory disease characterized by monoclonal gammopathy and recurrent episodes of urticaria accompanied by clinical and laboratory signs of acute inflammation. Interleukin (IL)-1 inhibitors proved to be useful in the treatment, but data on long-term safety and efficacy of these agents are sparse.Objectives:To evaluate the retention rate of IL-1 inhibitors in patients with Schnitzler’s Syndrome.Methods:Retrospective analysis of an Italian multicenter cohort (9 Centers). All patients fulfilled Strasbourg diagnostic criteria. Data are expressed as median [IQR].Results:We identified 15 patients (8 females, 7 males) who received a total of 24 treatment courses with IL-1 inhibitor treatment (16 anakinra and 8 canakinumab) between January 2001 and December 2019, with a median treatment duration of 19 months [8.5-51.3]. Median age at diagnosis was 64.0 years [56.0-72.5] and median follow up was 5.0 years [2.0-8.0]. Before the biological treatment, all patients were treated with corticosteroids and 11 with at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD): methotrexate (5), colchicine (5), cyclosporine (3), azathioprine (1), mycophenolate mofetil (1), cyclophosphamide (1).Fifteen patients received 16 courses of Anakinra, which was the 1st line biological treatment in 14 patients. Seven patients continued it with benefit, while 7 patients discontinued it: 3 for secondary inefficacy; 3 for adverse events (2 injection site reactions, 1 severe allergic reaction); 1 for secondary inefficacy and leukopenia. Anakinra was used as 2nd line treatment in 1 case (after tocilizumab failure); in 1 patient anakinra was resumed after temporary discontinuation and an attempt with infliximab. One patient died for multiple myeloma progression while on treatment with anakinra. The median duration of the courses with anakinra was 20.0 months [6.0-58.3].Seven patients received 8 courses of canakinumab (150 mg/8weeks in 5 cases and 150 mg/4weeks in 3). In 5 cases the drug was administered as 2nd line biological treatment (after anakinra failure) and in 2 cases as 3rd line treatment (1 after tocilizumab and anakinra failures and 1 after anakinra and adalimumab failure). In 1 patient, it was resumed after temporary discontinuation and an attempt with etanercept. One patient died while on treatment with canakinumab due to a presumably unrelated adverse event. The median duration of canakinumab treatment courses was 19.0 months [13.5-31.0].At last follow-up visit, all patients were on treatment with an IL-1 inhibitor: 8 with anakinra (7 at the dosage of 100 mg/day, 1 at the dosage of 200 mg/day) and 7 with canakinumab (2 at the dosage of 150 mg/8 weeks, 4 at the dosage of 150 mg/4 weeks and 1 at the dosage of 300 mg/4 weeks). Notably, in 3 patients the dosage of canakinumab was increased since the start of the treatment.Among 9 patients who were on treatment with prednisone at the start of the last IL-1 inhibitor, the prednisone median dose was 12.5 mg/day [10.0-18.8] while at the last follow-up visit it was 5.0 mg/day [0-7.5] (p= 0.02).The retention rate of IL-1 inhibitors was 73.4% [SE 9.4] at 1 year and 63.6% [SE 10.4] at 2 years (Figure 1a). There was no significant difference between the retention rate of anakinra (at 1 year: 67.0% [12.2]; at 2 years: 59.6% [12.9]) and canakinumab (at 1 year: 85.7% [13.2]; at 2 years 71.4% [17.1]) (log-rank test: p=0.41) (Figure 1b).Figure 1.a) Retention rate of IL-1 inhibitors (24 courses); b) Retention rate of canakinumab (8 courses) and anakinra (16 courses).Conclusion:In this multicentric cohort of patients affected by Schnitzler’s syndrome, the treatment with IL-1 inhibitors as 1st, 2nd or 3rd line biological treatment permitted a good disease control and corticosteroid reduction in patients who did not respond to csDMARDs and/or to prior other biological DMARDs. The optimal dosage of these drugs needs to be tailored for every patient.Acknowledgements:AIDA NetworkDisclosure of Interests:Francesca Crisafulli: None declared, Antonio Vitale: None declared, Carla Gaggiano: None declared, Lorenzo Dagna: None declared, Giulio Cavalli Speakers bureau: SOBI, Novartis, Paid instructor for: SOBI, Novartis, Consultant of: SOBI, Novartis, Rolando Cimaz: None declared, Ombretta Viapiana: None declared, Florenzo Iannone: None declared, Giuseppe Lopalco: None declared, Roberto Bortolotti: None declared, Masen Abdel Jaber: None declared, Carlomaurizio Montecucco: None declared, Sara Monti: None declared, Silvia Balduzzi: None declared, Giacomo Emmi: None declared, Paolo Airò: None declared, Franco Franceschini: None declared, Luca Cantarini Speakers bureau: SOBI, Novartis, Paid instructor for: SOBI, Grant/research support from: SOBI, Novartis, Micol Frassi: None declared

Different viral agents are associated with an increased risk of more severe disease course and respiratory complications in immunocompromised patients.1–3 The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) responsible for a severe acute respiratory syndrome (SARS) represents a source of concern for the management of patients with inflammatory rheumatic diseases. Lombardy is the region in Northern Italy with the highest incidence of COVID-19 cases, with more than 33 000 confirmed patients and 1250 requiring admission to the intensive care unit within 1 month. Since the first reports of COVID-19 cases in Italy, we have circulated a survey with a 2-week follow-up contact to patients with chronic arthritis treated with biological disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) followed up at our biological outpatient clinic in Pavia, Lombardy. The survey investigated the patients’ health conditions, the presence of contacts with subjects known to be affected by COVID-19 and management of …

Introduction Alveolar haemorrhage (AH) is considered an important cause of morbidity and early mortality in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV). Objectives The aim of this study was to identify predictors of outcome in patients with AH-AAV and to evaluate outcome and causes of death in this subset. Materials and methods A multicenter retrospective study was conducted in 29 Italian Centers. Clinicians were asked to recruit all patients diagnosed with AAV-associated AH during the last 10 years, from 2007 to 2016. Univariate and multivariable analysis were performed. Results One-hundred and six patients were included (median age at onset of 55 years [IQR 42–67]). The majority were ANCA-positive (PR3 57.1%, MPO 33.7%) and 72.6% had also renal involvement. At presentation, anaemia was shown in 97 (92.4%) patients, hemoptysis in 54 (51.9%), respiratory failure in 68 (66.7%), of whom 48 (70.6%), requiring respiratory support. At the end of the 37 months [IQR 13–77] follow-up, 19/106 (17.9%) patients were dead. The main causes of death were active disease and infections. By stepwise regression analysis, age >65 years (HR 3.66 [95% CI 1.4–9.51], p = 0.008) and the need for respiratory support (HR 4.58 [95% CI 1.51–13.87], p = 0.007) at AH onset were confirmed to be predictive of mortality. Conclusions Predictors of outcome in AAV-AH were determined. Factors related to the patient's performance status and the severity of the lung involvement strongly influenced the outcome. Balancing harms and benefits for the individual patient in induction and maintenance treatment strategies is crucial.

Background: Prevalence and outcomes of Coronavirus Disease (COVID)-19 in relation to immunomodulatory medications are still unknown. The aim of the study is to investigate the impact of glucocorticoids and immunosuppressive agents on COVID-19 in a large cohort of patients with chronic immune-mediated inflammatory arthritis. Methods: The study was conducted in the arthritis outpatient clinic at two large Academic Hospitals in the COVID-19 most endemic area of Northern Italy (Lombardy). We circulated a cross-sectional survey exploring the prevalence of Severe Acute Respiratory Syndrome-Coronavirus-2 nasopharyngeal swab positivity and the occurrence of acute respiratory illness (fever and/or cough and/or dyspnea), administered face-to-face or by phone to consecutive patients from 25th February to 20th April 2020. COVID-19 cases were defined as confirmed or highly suspicious according to the World Health Organization criteria. The impact of medications on COVID-19 incidence was evaluated. Findings: The study population included 2050 adults with chronic inflammatory arthritis receiving glucocorticoids, conventional-synthetic (cs), or targeted-synthetic/biological (ts/b) disease-modifying drugs (DMARDs). Laboratory-confirmed COVID-19 and highly suspicious infection were recorded in 1.1% and 1.4% of the population, respectively. Treatment with glucocorticoids was independently associated with increased risk of COVID-19 (adjusted OR [95% CI] ranging from 1.23 [1.04-1.44] to 3.20 [1.97-5.18] depending on the definition used). Conversely, patients treated with ts/bDMARDs were at reduced risk (adjusted OR ranging from 0.46 [0.18-1.21] to 0.47 [0.46-0.48]). No independent effects of csDMARDs were observed. Interpretation: During the COVID-19 outbreak, treatment with immunomodulatory medications appears safe. Conversely, glucocorticoids, even at low-dose, may confer increased risk of infection. Funding: None. Declaration of Interests: Authors declare no competing interest. Ethics Approval Statement: The current analysis was approved by the Ethics Committees of the Gaetano Pini Institute and Policlinico San Matteo as part of a project to collect observational data from rheumatological patients followed at the two involved rheumatology units. All included patients have signed an informed consent to participate in the data collection. The possibility of including this survey within the abovementioned data collection project has been waived by the same ethics committee.

To evaluate the clinical effectiveness of golimumab in biologic inadequate responder (IR) patients with Rheumatoid arthritis (RA), Spondyloarthritis (SpA), and Psoriatic arthritis (PsA).We analyzed 1424 patients on golimumab from the GISEA registry. Drug survival was estimated by Kaplan-Meier analysis in biologic-naïve, 1-biologic IR, ≥2-biologics IR patients. Hazard ratios (HRs) of discontinuing golimumab at 2 years were assessed by multivariate Cox regression. Patients achieving CDAI based low disease activity (LDA) or BASDAI4 were calculated at 6 and 12 months.In RA (n.370), the 2-years survival on golimumab was 61.4% in 1-biologic IR, 51.9% in≥2-biologics IR, and 73.1% in biologic-naive patients (P=0.002 vs≥2-biologics IR). In SpA (n.502), the survival was similar among 1-biologic IR (80%), ≥2-biologics IR (76.5%), and biologic-naive (74.6%) patients (P0.05). In PsA (n.552) the survival was 72% in 1-biologic IR, 72.5% in≥2-biologics IR, and 71.8% in naïve-biologic (P0.05). Predictors of golimumab discontinuation were monotherapy (HR 1.65) for RA, female gender for SpA (HR 2.48) and PsA (HR 1.57). In RA, patients on CDAI-LDA were lower in 1-biologic IR (40%) or≥2 biologics IR (40%) than in biologic-naïve (60%) group at 6 months (P=0.02), but no difference was observed at 12 months. In PsA and SpA, the percentage of patients on CDAI-LDA or BASDAI4 at 6 months was almost identical across the subgroups.Golimumab had similar effectiveness in biologic-failure and biologic-naïve SpA and PsA, but seems to be less effective in multi-failure RA patients, especially as monotherapy. The best outcomes were seen in male patients.

In light of their increased risk of worst outcomes following COVID-19 infection, patients with rheumatic and musculoskeletal diseases (RMDs) on immunosuppressive therapy, including systemic glucocorticoids, biological (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs), represent a vulnerable population which should be prioritised to receive vaccination. Controlled data on the effectiveness and safety of different COVID-19 vaccines on patients with RMD are not available yet. However, rheumatology providers and health professionals should be ready to offer timely guidance for the optimal use of vaccines for patients on immunomodulatory drugs. Based on the long-time experience with other non-live vaccines, the COVID-19 Task Force of the European League Against Rheumatisms (EULAR) first delivered a preliminary set of information in December 2020.1 Overall, it is expected that the safety and immunogenicity of COVID-19 vaccines for most of the DMARDs will be comparable with that registered for the general population,2–4 so that postponing vaccination pending more information appears unjustified. A number of independent surveys have however alarmingly reported that, among patients with RMD, potential acceptance of COVID-19 vaccines may not exceed 60%, without apparent differences in relation to specific diseases, comorbidities and type of medication.5–8 Strategies to effectively engage high-risk patients with RMD into vaccination programmes are therefore urgently needed. Starting from 19 March 2021, rheumatologists of the IRCCS Policlinico San Matteo University Hospital of Pavia, Italy, have been actively involved in the vaccination campaign by personally contacting, booking and administering COVID-19 vaccines to patients with RMD on b/tsDMARDs followed at …

Objective Arthritis, myositis and interstitial lung disease (ILD) constitute the classic clinical triad of anti-synthetase syndrome (ASSD). These patients experience other accompanying features, such as Raynaud's phenomenon, fever or mechanic's hands. Most ASSD patients develop the complete triad during the follow-up. In the present study we aimed to determine whether the subsequent appearance of accompanying features may suggest the development of triad findings lacking at the onset in anti-Jo1 positive ASSD patients. Methods Anti-Jo1 positive patients presenting with incomplete ASSD (no >2 classic triad features) were assessed. Clinical characteristics and clusters of disease manifestations were retrospectively collected and analyzed in a large international multicenter cohort of ASSD patients. Results 165 patients (123 women) with incomplete ASSD were identified. Ninety-five patients (57.5%) developed new classic triad manifestations after 15months median (IQR 9–51) and 40 (24%) developed new accompanying features after 19months median (IQR 6–56) from disease onset. During the follow-up, the ex-novo occurrence of triad features was observed in 32 out of 40 patients (80%) with new accompanying findings and in 63 out of 125 patients (50.5%) without new accompanying findings (p=0.002). In patients with at least one new accompanying feature the odds ratio for the occurrence of new triad manifestations was 3.94 with respect to patients not developing ex-novo accompanying findings (95% CI 1.68–9.21, p=0.002). Conclusion Anti-Jo1 ASSD patients with incomplete forms at disease onset are at high risk for the subsequent occurrence of lacking classic triad findings. Although all ASSD patients should be carefully assessed for the occurrence of new triad features, a closer follow-up should be considered in the subgroup of patients developing ex novo accompanying findings. These patients, indeed, have near four-fold increased risk for new classic triad manifestation occurrence with respect to patients not presenting ex novo accompanying findings.

Background:Observational data on the use of secukinumab for the treatment of spondyloarthritides are still lacking. Large population-based registries that allow long-term follow-up have been increasingly used to investigate the performance of biologic drugs in a real life setting.Objectives:The aim of this study is to evaluate the effectiveness and the retention rate of secukinumab in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients in a real-life setting over a 3-year follow-up period.Methods:Data of all PsA and axSpA patients (diagnosed according to CASPAR and ASAS criteria, respectively) treated with secukinumab were prospectively collected in the Italian multicentric LORHEN registry. Effectiveness was measured as the mean change from baseline of Disease Activity in PSoriatic Arthritis score (DAPSA) in PsA and Ankylosing Spondylitis Disease Activity Score (ASDAS) in axSpA patients. Rates of DAPSA remission and ASDAS inactive disease were also computed. The 3-year retention rate was calculated by the Kaplan-Meier method and compared between PsA and axSpA by a log-rank test. A descriptive analysis of reasons for discontinuation was performed.Results:The study population included 195 PsA (55.4% females, mean age 50.7 [±11.8] years, mean disease duration 10 [±7.8] years, mean baseline DAPSA 23.12 [±12.3]) and 94 axSpA (61.7% males, mean age 49.1 [±12.7] years, mean disease duration 10.4 [±9.4] years, mean baseline ASDAS 3.41 [±1.1]) patients who received secukinumab as first (26.5 and 33%, respectively) or subsequent biologic agent. Compared with baseline, the 3-, 6- and 12-month mean values of both DAPSA (12.6 [±9], 11.2 [±10.5] and 9.3 [±7.5], respectively) and ASDAS (2.23 [±0.9], 2.15 [±0.9], and 1.84 [±0.9], respectively) were significantly decreased (pConclusion:Our data confirmed in a real-life setting the 1-year clinical efficacy and the 3-year survival of secukinumab in both PsA and axSpA. The safety profile of secukinumab was very favorable for both the indications. No significant differences were observed in the performance of secukinumab between ax-SpA and PsA.References:[1]Deodhar A, et al. Arthritis Research & Therapy; 2019.[2]Mease PJ, et al. RMD Open. BMJ Specialist Journals; 2018;4(2):e000723.[3]Baraliakos X, et al. Clin Exp Rheumatol. 2018 Jan;36(1):50–5.Disclosure of Interests:Ennio Giulio Favalli Consultant of: Consultant and/or speaker for BMS, Eli-Lilly, MSD, UCB, Pfizer, Sanofi-Genzyme, Novartis, and Abbvie, Speakers bureau: Consultant and/or speaker for BMS, Eli-Lilly, MSD, UCB, Pfizer, Sanofi-Genzyme, Novartis, and Abbvie, Antonio Marchesoni Speakers bureau: Abbvie, Pfizer, UCB, Novartis, Celgene, Eli Lilly, Silvia Balduzzi: None declared, Carlomaurizio Montecucco: None declared, Claudia Lomater Consultant of: Advisory board for Sanofi, Novartis, Abbvie, Gloria Crepaldi Consultant of: Advisory board for Sanofi and Celgene, Speakers bureau: BMS, MSD, Silvia Talamini: None declared, Chiara Bazzani: None declared, Enrico Fusaro: None declared, Marta Priora: None declared, Aurora Iannello: None declared, Giuseppe Paolazzi: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB

Diffuse alveolar haemorrhage (DAH) secondary to anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a rare life-threatening condition presenting with severe respiratory failure. The management of AAV-related DAH consists of remission induction immunosuppressive therapy, which requires time to be effective, with significant fatality rates despite appropriate treatment. Extracorporeal membrane oxygenation (ECMO) can support gas exchanges providing the time necessary for immunosuppressive treatment to control the underlying disease in cases refractory to the conventional ventilation techniques. Despite severe preexisting bleeding has been considered a relative contraindication, ECMO has proven to be life-saving in several cases of respiratory failure associated with pulmonary haemorrhage due to various causes, including AAV. We reviewed the clinical presentation and course of two patients affected by AAV-related DAH treated at our Institution between 2012 and 2017, whose management required the use of veno-venous ECMO. We reviewed the current literature on the role of ECMO in the support of these patients. In both patients, ECMO provided life support and allowed disease control, in combination with immunosuppressive treatment. Despite systemic anticoagulation, clinical improvement was achieved without exacerbation of the pulmonary bleeding. We performed a literature review, and summarized available data confirming the effectiveness and safety of ECMO in AAV-related DAH. ECMO has a life-saving role in the management of patients with severe respiratory failure due to ANCA-associated pulmonary capillaritis.

Background Diffuse alveolar haemorrhage (DAH) is a rare and severe manifestation of ANCA-associated vasculitides (AAV). Objectives To identify predictors of survival in patients with AAV-DAH. Methods A retrospective study of 102 consecutive patients (50% females; mean age 59±17 years) from 27 Italian Centres diagnosed with AAV-DAH was planned. Cox regression unadjusted analyses were performed. Results Among AAV patients, 47% had Granulomatosis with Polyangiitis (GPA), 47% Microscopic Polyangiitis (MPA) and 6% Eosinophilic Granulomatosis with Polyangiitis (EGPA). At DAH onset, mean BVAS was 20±8 and most patients had renal involvement (RI). Admission to Intensive Care Unit was needed in 27% of patients, while ventilatory support (VS) was required in 46%. At least one cardiovascular risk factor (CVRF) was recorded in 48%. Over a median follow-up of 39 months (25%–75% IQR 66 months), 19/102 patients (18.6%) died (figure 1). All patients received high-dose glucocorticoids in association with Cyclophosphamide (CYC 78%, mean cumulative dose 8±7 g) or Rituximab (37%). Plasma exchange was performed in 46%. Infections occurred in 38%. Age>65 years (HR 3.05 [95% CI 1.18–7.9], p=0.04), CVRF ≥2 (HR 8.85 [95% CI [AG7] 2.34–33.50], p=0.01), BVAS (v.3) (HR 1.07 [95% CI 1.01–1.13], p=0.01) were associated with mortality, whereas FFS was not. The need for VS (HR 4.54 [95% CI 1.48–13.85], p=0.008) and infections (HR 3.98 [95% CI 1.48–10.69] were also associated with mortality. Conclusions Older age, VS, CVRF and infections affect the survival in AAV. There is a need for specific outcome measeures. Disclosure of Interest None declared

Background The optimal duration of remission-maintenance treatment in ANCA-associated vasculitis (AAV) is still unknown, 1 with International recommendations suggesting to maintain it for at least 24 months. Data supporting the correct balance between relapse risk, treatment-related adverse events and damage are highly needed. Objectives To analyse the frequency and predictors of withdrawal of remission-maintenance immunosuppressive drugs (IS) in a large real-life cohort of AAV patients. Methods Clinical records of patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) were retrospectively analysed from a multicentric cohort. We divided the cohort into group A (withdrawal) and group B (ongoing). Results We included 185 patients. Forty-one patients (22%) had withdrawn IS at the end of follow-up (median 73.5 months, IQR 54–115). Concomitant glucocorticoids were stopped in 33%. There were no significant differences in AAV subtype, ANCA pattern, age at diagnosis, diagnostic delay or comorbidities rates between group A and group B (table 1). Disease onset with pulmonary involvement was significantly more frequent in patients in whom IS was maintained (69.7% vs 45%; p=0.004). Figure 1. Disease activity at onset, but not during follow-up, was significantly higher in patients from group B (ongoing): median BVAS 18 (12–24) vs 15; (8–20) p=0.02. The type of IS used for remission induction did not differ between the two groups. Maintenance treatment with Rituximab (RTX) was associated with higher probability of discontinuing IS by the end of follow-up (21% vs 7.6%; p=0.02). There was no difference in the number of major relapses between the two groups. Safety profile was equally good in both groups, except for a higher number of infections over the course of disease in patients who withdrew IS (5% vs 0). Vasculitis damage index (VDI) was comparable between the two groups. Conclusions IS withdrawal was observed in a minority of real-life patients with AAV. Drug-free remission was negatively associated with pulmonary involvement and higher BVAS at disease onset. Remission maintenance with RTX was associated with a higher frequency of drug withdrawal at the end of follow-up. Reference [1] Karras, et al. Randomised controlled trial of prolonged treatment in the remission phase of ANCA-associated vasculitis. Ann Rheum Dis2017;76:1662–68 Disclosure of Interest None declared

Background ANCA specificity, rather than clinical diagnosis, has been suggested to influence the phenotype and clinical course of ANCA associated vasculitis (AAV) (1,2). Objectives To investigate differences in clinical presentation at disease onset between MPO-ANCA-positive granulomatosis with polyangiitis patients (MPO-GPA), PR3-ANCA-positive-GPA (PR3-GPA), and MPO-ANCA-positive microscopic polyangiitis (MPO-MPA). Methods Clinical records of AAV patients from three third level rheumatologic centers in Northern Italy were retrospectively analyzed. Results Of the 133 AAV patients included, 84 were PR3-GPA, 24 MPO-GPA, and 25 MPO-MPA. Patients with MPO-MPA were significantly older at diagnosis compared to both PR3-GPA and MPO-GPA (average age 63±10, 49±15, 55±29, respectively) (Table 1). Patients with MPO-GPA experienced a significant diagnostic delay compared to PR3-GPA (17±30 vs 7±14, p=0.02). ENT involvement was equally frequent in both GPA groups despite ANCA specificity, and significantly more represented than the MPO-MPA group (68%, 71% and 17% respectively; p Conclusions Clinical phenotype of GPA at disease onset did not seem to be influenced by ANCA specificity. Despite ANCA positivity (PR3 or MPO), GPA patients were significantly different from MPA. References Schirmer JH, Wright MN, Herrmann K, et al. Myeloperoxidase-Antineutrophil Cytoplasmic Antibody (ANCA)-Positive Granulomatosis With Polyangiitis (Wegener9s) Is a Clinically Distinct Subset of ANCA-Associated Vasculitis: A Retrospective Analysis of 315 Patients From a German Vasculitis Referral Center. Arthritis Rheumatol Hoboken NJ 2016;68:2953–63. Miloslavsky EM, Lu N, Unizony S, et al. Myeloperoxidase-Antineutrophil Cytoplasmic Antibody (ANCA)-Positive and ANCA-Negative Patients With Granulomatosis With Polyangiitis (Wegener9s): Distinct Patient Subsets. Arthritis Rheumatol 2016;68:2945–2952. Disclosure of Interest None declared

Background The clinical phenotype of the antisynthetase syndrome (AS) has been related with the underlying autoantibody specificity. The typical disease triad (arthritis, myositis, and interstitial lung disease -ILD) is common in anti Jo-1 + AS, whereas isolated ILD is associated with anti PL-7 and PL-12 Ab. The majority of anti Jo-1 + patients without all triad findings at the onset (incomplete ASSD) will develop lacking features during the followup Objectives To assess the triad clinical spectrum time course in non anti Jo-1 + AS Methods The study cohort included patients + for anti-EJ, OJ, PL-7, or PL-12 Ab with at least 1 triad finding. Clinical features were retrospectively collected and analyzed Results we included 65 non anti Jo-1 + AS (7 anti EJ, 4 anti OJ, 30 anti PL-12, 24 anti PL-7; 49 females, 16 males). In median, age at disease onset was 53 years (IQR 42–64), diagnostic delay 9 months (IQR 3–23.5), followup 60 months (IQR 20.5–113). Patients9 characteristics are reported in Table 1. During the followup, 22/61 patients with incomplete AS developed new triad findings, in median 12 months (IQR 6–27) after disease onset. The frequency of incomplete AS developing new triad findings and the length of followup were significantly reduced in non anti Jo-1 + patients with respect to our corresponding anti Jo-1 + cohort (respectively: 22/61 vs 138/220, p Conclusions In non anti Jo-1 + patients the ex novo occurrence of classic triad finding is common, but less frequent than in anti Jo-1 + patients. The different length of followup may explain at least partly this difference References Cavagna L, et al. Medicine (Baltimore) 2015;94:e1144 Disclosure of Interest None declared

Background Early diagnosis and early treatment with DMARDs lead to better outcomes in rheumatoid arthritis (RA) (1,2). The 2010 ACR/EULAR criteria for RA were developed for early classification (3) and have good sensitivity, lower specificity and overall moderate accuracy. Their usefulness to lead treatment selection has not been investigated yet. Objectives To compare clinical remission (CR) rates in patients with early polyarthritis in which the decision to start methotrexate (MTX) was based on the 1987 ACR vs 2010 ACR/EULAR criteria, over the first 12 months follow up. Methods This is an observational non concurrent cohort study. Patients classified as RA or undifferentiated arthritis (UA) attending for the first time our early arthritis clinic (2005-2013) were eligible for inclusion. At baseline, before October 2010, patients classified as RA according to the 1987 criteria were treated with MTX (from 10 mg/wk up to 20 mg/wk), while patients with UA received hydroxychloroquine (HCQ) (1987 cohort). After October 2010, patients fulfilling the 2010 criteria received MTX (from 15 mg/wk up to 25mg/wk), while UA received HCQ (2010 cohort). Low-dose prednisone could be given according to clinician9s decision. Patients were seen every 2 months in the first six months and every 3 afterwards; treatment was increased in order to achieve low disease activity (DAS28 Results Out of 676 patients, 467 were included in the 1987 cohort and 209 in the 2010 cohort. There were no significant differences between the two cohorts in terms of age, gender, VAS pain, RF and ACPA positivity. Patients in the 2010 cohort had significantly fewer median (IQR) tender (4 (2-8) vs 5 (2-10), p=0.018) and swollen joints (4 (2-7) vs 6 (3-10), p Conclusions Patients with early arthritis in which the decision to start MTX is driven by the 2010 criteria achieve more often CR compared to those treated according to the 1987 criteria. Beside the limited diagnostic accuracy of the 2010 criteria, these results support their usefulness as treatment selection guidance in practice. References Sakellariou G et al, Ann Rheum Dis 2013;72:245-9 Breedveld FC et al, Arthritis Res Ther 2011;13:S3 Aletaha et al, Ann Rheum Dis 2010;69:1580-8 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4987

Background As a consequence of the 2010 classification criteria for rheumatoid arthritis (RA) the definition of undifferentiated arthritis (UA) has changed, identifying different clinical patterns (1). Ultrasonographic (US) features and predictors of response in this population have not been described yet. Objectives To evaluate the clinical and US features in patients with UA according to the 2010 criteria, the occurrence of clinical remission in the first 12 months of treatment and its clinical and US predictors. Methods Patients attending an early arthritis clinic (2005-2012) with a 2010 classification criteria score Results A total of 215 patients were included. Median (IQR) follow-up was 12 (6-12) months, mean (sd) age 56.8 years (15.07), 64 patients (29.7%) were male, mean DAS28 was 3.74 (0.95). The median score of the 2010 criteria was 4 (4-5). At baseline HCQ was given to 169 (78.6%) patients and prednisone to 87 (40.5%). The median GS and PD scores were 4 (2-17) and 1 (0-14), respectively. Within the first year of observation 124 (57.7%) patients achieved clinical remission at least once. Remission was less likely in older (HR 0.98 (0.97,0.99)p=0.014) and female (HR 0.64 (0.45,0.90), p=0.012) patients. High titers of anti-citrullinated peptide antibodies and/or rheumatoid factor predicted remission (HR 3.34 (1.30,8.57) p=0.012), while the remaining items of the criteria did not. Among US variables, a baseline PD score>0 (HR 1.75 (1.06,2.88) p=0.027) or a PD score>1 (HR 1.68 (1.03,2.72) p=0.036), the presence of at least one joint with PD>1 (HR 1.81 (1.07,3.06), the count of joints with PD>0 (HR 1.15 (1.03,1.28) p=0.012) and PD>1 (HR 1.30 (1.05,1.61)) and the overall PD score (HR1.10 (1.02,1.18) p=0.011) predicted subsequent clinical remission. Conclusions High-titer autoantibodies (2) and PD identify UA patients that are more likely to reach clinical remission when treated. These features might be useful to drive the decision to start treatment in early UA. References Krabben A, et al. Ann Rheum Dis 2012;71:238-41. Wevers-de Boer K, et al. Ann Rheum Dis 2012;71:1472-7. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5046