C Adamichou

Low disease activity—irrespective of serologic status at baseline—associated with reduction of corticosteroid dose and number of flares in patients with systemic lupus erythematosus treated with belimumab: A real-life observational study

BACKGROUNDnLow disease activity is a validated target of current systemic lupus erythematosus (SLE) therapy. The aim of this study was to assess the ability of belimumab to achieve low disease activity states in real-life settings.nnnMETHODSnMulticentre prospective observational study of consecutive SLE patients receiving belimumab for at least 3 months, due to active disease refractory to at least one conventional immunosuppressant. Disease activity, including the recently defined lupus low disease activity state (LLDAS) and remission (clinical SLEDAI-2K = 0), accrual of organ damage, flares and side effects were documented.nnnRESULTSnNinety-one patients were included [94.5% women, mean (SD) age 45.9 (12.5) years]. Most frequent manifestations were arthritis (76.7%), rash (72.5%), serologic activity (low C3/C4 and/or high anti-dsDNA; 54.9%), hair loss (47.2%) and mucosal ulcers (27.5%). Median (range) duration of treatment was 10.5 (3.0-42.1) months. Belimumab significantly decreased average SLEDAI-2K, physician global assessment (PGA) and daily prednisone dose over time, as early as 3 months after initiation, with over 20% of patients discontinuing corticosteroids. Although reduction in clinical (i.e., excluding serology) SLEDAI-2K was more pronounced in patients who were serologically active (from 8 to 1.5 at 12 months) as compared to serologically inactive (from 6 to 4) at baseline, attainment of LLDAS did not differ between the two groups and was reached by more than 40% of completer patients after 9-12 months. In addition, the number of flares and severe flares was reduced by 62% and 50%, respectively, during the first 12 months of treatment. Twenty patients (22.0%) discontinued treatment due to inadequate response and two due to side effects potentially related to the drug.nnnCONCLUSIONSnIn real-life, belimumab is efficacious in achieving low disease activity in over 40% of unselected patients, in combination with reduction of corticosteroid dosage and number of flares. Both serologically active and inactive patients respond to the drug.

Epidemiology and burden of systemic lupus erythematosus in a Southern European population: data from the community-based lupus registry of Crete, Greece

Objectives Several population-based studies on systemic lupus erythematosus (SLE) have been reported, yet community-based, individual-case validated, comprehensive reports are missing. We studied the SLE epidemiology and burden on the island of Crete during 1999–2013. Methods Multisource case-finding included patients ≥15 years old. Cases were ascertained by the ACR 1997, SLICC 2012 criteria and rheumatologist diagnosis, and validated through synthesis of medical charts, administrative and patient-generated data. Results Overall age-adjusted/sex-adjusted incidence was 7.4 (95%u2009CI 6.8 to 7.9) per 100 000 persons/year, with stabilising trends in women but increasing in men, and average (±SD) age of diagnosis at 43 (±15) years. Adjusted and crude prevalence (December 2013) was 123.4 (113.9 to 132.9) and 143 (133 to 154)/105 (165/105 in urban vs 123/105 in rural regions, p<0.001), respectively. Age-adjusted/sex-adjusted nephritis incidence was 0.6 (0.4 to 0.8) with stable trends, whereas that of neuropsychiatric SLE was 0.5 (0.4 to 0.7) per 100u2009000 persons/year and increasing. Although half of prevalent cases had mild manifestations, 30.5% developed organ damage after 7.2 (±6.6) years of disease duration, with the neuropsychiatric domain most frequently afflicted, and 4.4% of patients with nephritis developed end-stage renal disease. The ACR 1997 and SLICC 2012 classification criteria showed high concordance (87%), yet physician-based diagnosis occurred earlier than criteria-based in about 20% of cases. Conclusions By the use of a comprehensive methodology, we describe the full spectrum of SLE from the community to tertiary care, with almost half of the cases having mild disease, yet with significant damage accrual. SLE is not rare, affects predominantly middle-aged women and is increasingly recognised in men. Neuropsychiatric disease is an emerging frontier in lupus prevention and care.

PS3:51 Multimorbidity burden in sle: preliminary data from the community-based lupus registry of crete

Purpose To examine the prevalence of comorbidities in SLE patients at the community as well as their impact on disease outcomes.1 Methods We utilised data from the Cretan Lupus Registry.2 Comorbidities were defined based on self-reported condition(s) and/or use of relevant treatments, and were accessed through face interviews upon enrollment (period 2012–2015). Data on organ damage (SLICC/ACR Damage Index [SDI]), disease severity (modified BILAG index) and hospitalizations were abstracted from the medical charts. Results We included 399 SLE patients with mean age at diagnosis 43 years and disease duration 7 years. The total number of comorbidities was (mean ±SD) 3.4±2.4u2009and 42% of patients had multi-morbidity (>3 comorbidities). The mean Charlson Comorbidity Index was 0.9±1.1. The prevalence of major comorbidities in SLE patients and their co-occurrence matrix are shown in Figure 1 and Table 1, respectively. Most frequent physical comorbidity was thyroid disease (45%), which frequently (19%) concurred with a mental disorder. Although 36% of patients reported mental disorders, only 14% were regularly seen by a mental health professional. Female SLE patients had increased frequency of thyroid (51% versus 16%, p<0.001), allergic diseases (21% versus 3%, p=0.006), and osteoporosis (19% versus 6%, p=0.05) compared to male patients, whereas respiratory comorbidities (21% versus 9%, p<0.001) and alcohol abuse (3% versus 0%, p<0.01) were more prevalent among male patients. Analysis according to the place of residence revealed increased prevalence of respiratory comorbidities among patients who reside in rural (12.3%) versus urban (7.2%) or semi-urban (7.7%) regions (p=0.014). SLE patients with multi-morbidity had more hospitalizations due to active disease (2.2±5.8u2009versus 1.1±2.3, p<0.001) and increased organ damage accrual (SDI>0) (40.8% versus 28.5%, p=0.044) compared to those with ≤3 comorbidities. In multivariable analysis, age-adjusted Charlson Comorbidity Index was associated with disease severity (Odds Ratio 1.43, p<0.003) Conclusions Our results from a community-based registry highlight a considerable burden of physical and mental multi-morbidity in SLE patients, which may be linked to adverse disease outcomes.Abstract PS3:51 Table 1 Prevalence and combinations of main comorbidities of SLE patientsAbstract PS3:51 Figure 1 Prevalence of physical (1A) and mental comorbidities (1B) of SLE patients (n=399) at the community level (cretan lupus registry) References . Expert Rev Clin Immunol2017;13(8):753–768. . Gergianaki I, et al. Ann Rheum Dis2017.

Cytokine targets in lupus nephritis: Current and future prospects

Despite advancements in the care of lupus nephritis, a considerable proportion of patients may respond poorly or flare while on conventional immunosuppressive agents. Studies in murine and human lupus have illustrated a pathogenic role for several cytokines by enhancing T- and B-cell activation, autoantibodies production and affecting the function of kidney resident cells, therefore supporting their potential therapeutic targeting. To this end, there is limited post-hoc randomized evidence to suggest beneficial effect of belimumab, administered on top of standard-of-care, during maintenance therapy in lupus nephritis. Type I interferon receptor blockade has yielded promising results in preliminary SLE trials yet data on renal activity are unavailable. Conversely, targeting interleukin-6 and interferon-γ both failed to demonstrate a significant renal effect. For several other targets, preclinical data are encouraging but will require confirmation. We envision that high-throughput technologies will enable accurate patient stratification, thus offering the opportunity for personalized implementation of cytokine-targeting therapies.

Flares in systemic lupus erythematosus: diagnosis, risk factors and preventive strategies

Despite advances in the treatment, patients with systemic lupus erythematosus (SLE) often experience disease exacerbations (flares) of varying severity. Their diagnosis is primarily made on clinical grounds after exclusion of other diseases or disturbances, primarily infections, and can be assisted by the use of validated clinical indices. Serological tests such as serum complement fractions and anti-dsDNA autoantibodies, are helpful in monitoring SLE activity, but they lack high diagnostic accuracy. Flares are more frequent in patients with persistent immunological and clinical activity, and have been described as significant risk factor for development of irreversible end-organ damage. Accordingly, prevention of flares has been recognized as a distinct therapeutic target in SLE and involves adequate control of disease activity, use of hydroxychloroquine, maintaining immunosuppressive or biologic therapy for several years, and avoiding non-compliance issues. The future holds promise for the discovery of biomarkers that will accurately predict or diagnose SLE flares, thus allowing for the implementation of patient-tailored preventive strategies.

SAT0204 Abatacept survival in rheumatoid arthritis patients at 2 years is 59%; its use as a 2nd line biologic agent and lower baseline haq predict better survival in clinical practice: a prospective, observational single center study

Background Long-term prospective observational studies are complementary to controlled clinical trials to explore effectiveness and safety of biological therapies in clinical practice. Objectives To study abatacept survival, reasons of discontinuation and clinical responses in everyday clinical practice of patients with rheumatoid arthritis (RA). Methods Prospective, observational single center study at the Rheumatology Clinic, University Hospital of Heraklion, Crete. At baseline, patient demographics, co-morbidities and disease characteristics are being recorded, while during follow-up, discontinuations, disease activity and adverse events are collected. For this analysis, all patients who received Abatacept intravenously from 6/2007 till 6/2016 were included. Kaplan-Meier curves and Cox regression analysis were used to determine drug survival and predictors thereof. Linear regression was used to compare DAS difference at 12 months between different lines of bDMARD therapy. Results A total of 224 patients (women: 87%, seropositive: 34%) were included. Median (IQR) age was 63 (56–70) years, disease duration 7.4 (4–13.4) years and baseline DAS28 5.9 (5.2–6.5). Abatacept was the 1st bDMARD in 59 (26%), 2nd in 71 (32%) and ≥3rd in 94 (42%) patients. During follow-up [total: 508 patient-years, median (IQR): 1.7 (0.7–3.3) years], 54% patients discontinued therapy (87% for treatment failure, 10% for adverse events). Two-year treatment persistence was 59%. In multivariable regression analysis, predictors of longer Abatacept survival were lower baseline HAQ [HR (95% CI) for unit increase =2.29 (1.5–3.48), p<0.001], longer disease duration [HR (95% CI) for ≥8 vs.<8 years=0.51 (0.30–0.88), p=0.016], Abatacept as 2nd vs 1st or ≥3rd bDMARD [HR =0.52 (0.30–0.91), p=0.022] and a more recent year of therapy start [HR=0.39 (0.16–0.95), p=0.022]. DAS28<3.2 and remission at 6 (12) months were achieved by 12% (18%) and 5% (7%) of patients respectively. DAS28 difference at 12 months was greater in patients who received Abatacept as the ≤2nd than those on ≥3rd bDMARD (p=0.009). A total of 312 adverse events were registered, of which 65 were serious (SAE). Incidence of total (serious) adverse events was 61 (13) /100 patients/year. SAE included 5 cases of cancer, 10 cardiovascular events and 24 infections, mainly of the respiratory tract. Conclusions In the present study, Abatacept survival at 2 years was 59%. The majority of patients discontinued therapy due to inadequate response. Use as a 2nd line biologic agent and lower baseline HAQ predicted better survival. Improvement in DAS was higher when Abatacept was used as the ≤2nd bDMARD. Rates of remission or low disease activity in clinical practice are rather low, while the safety profile was excellent. Disclosure of Interest None declared

AB0442 Real-life experience with belimumab in systemic lupus erythematosus (SLE): control of disease activity and flares in a multicenter cohort

Background Data on the efficacy of belimumab in SLE mainly originate from large randomized clinical trials, whereas reports from real-life clinical practice are lacking. Objectives To describe the clinical experience from the use of belimumab in Greece since the approval of the drug. Methods Multicentre observational study of patients receiving belimumab, with documentation of disease activity (SLEDAI-2K index), achievement of low disease activity states [remission (SLEDAI-2K=0) and lupus low disease activity state (LLDAS)], accrual of irreversible damage (SLICC damage index, SDI), number and severity of flares, and side-effects. Analyses were performed at quarterly intervals and only patients with at least 3 months of follow-up were included in the study. Results A total of 56 patients were included [53 women (94.6%), mean (SD) age 46.3 (12.7) years]. Evidence of serologic activity (low C3/C4 and/or high anti-ds DNA) was evident in 30 patients (53.5%). Most frequent manifestations were arthritis (82.1%), inflammatory rash (73.2%), active hair loss (57.1%), mucosal ulcers (26.8%) and leukopenia (10.7%). Median (range) duration of follow-up was 9.1 (2.9 - 34.6) months. We observed a significant decrease in the SLEDAI-2K, physician global assessment (PGA) and daily prednisone dose over time, starting as early as 3 months after belimumab initiation (Table 1). This effect was significantly more pronounced in patients who were serologically active (SA) at baseline, even after exclusion of the serologic component of the SLEDAI [median (range) clinical SLEDAI-2K for SA patients: 7 (1–24) at baseline vs. 2 (0–16) at 6 months and 2 (0–16) at 12 months, p<0.0001 and p=0.013, respectively; for serologically inactive patients: 6 (2–23) at baseline vs. 6 (0–14) at 6 months and 5 (0–18) at 12 months, p=0.017 and p=0.024, respectively]. For patients with ≥12 months of follow-up (n=20), belimumab treatment resulted in a significant decrease in flare rate [median (range) total number of flares for the 12 months before and after belimumab treatment, 3 (0–7) and 0 (0–2), respectively, p<0.0001). 10 patients (17.8%) discontinued belimumab due to inefficacy after a median (range) 7.1 (5.5 - 20.4) months of therapy and 5 patients discontinued due to planned pregnancy. There were no drug discontinuations due to side-effects. Conclusions In real-life clinical settings, belimumab is efficacious in controlling disease activity of SLE and permitting tapering of glucocorticoid dose. Similar to data from RCTs, this effect seems to be more pronounced in serologically active patients. Disclosure of Interest None declared