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We present a case of a 75-year-old woman who admitted in the internal medicine department for a recent onset of persisting moderate daily fever and fatigue that started 30 days prior to her hospitalization. Her past medical history is remarkable for mild pulmonary fibrosis, megaloblastic anaemia, and hypergammaglobulinaemia of no obvious causes. On presentation, she was febrile (38ºC) and had high ESR and CRP levels, but most of her laboratory tests were within normal levels and had no signs of arthritis or rash. She was hospitalized for suspected lower urinary tract infection and started on antibiotics. During hospitalization, her renal function deteriorated together with microscopic haematuria, proteinuria and granular urine casts in urine analysis and her inflammation markers raised further. A renal biopsy revealed glomerulonephritis with pauci-immune crescents, and serology tests were positive for anti-MPO p-ANCA, both suggesting a diagnosis of microscopic polyangiitis (MPA). While high-dose methylprednisolone pulses and cyclophosphamide were introduced intravenously, there was no remission, but respiratory failure occurred that led to patient's intubation and transfer to the ICU. She died a few days later due to septic shock. Asymptomatic pulmonary fibrosis can precede microscopic polyangiitis for several years and is associated with a poor prognosis.

ObjectiveTo obtain real-world data on outcomes of belimumab treatment and respective prognostic factors in patients with systemic lupus erythematosus (SLE).MethodsObservational study of 188 active SLE patients (median disease duration 6.2 years, two previous immunosuppressive/biological agents) treated with belimumab, who were monitored for SLEDAI-2K, Physician Global Assessment (PGA), LLDAS (lupus low disease activity state), remission (DORIS/Padua definitions), SELENA-SLEDAI Flare Index, SLICC/ACR damage index and treatment discontinuations. Group-based disease activity trajectories were modelled followed by multinomial regression for predictive variables. Drug survival was analysed by Cox-regression.ResultsAt 6, 12 and 24 months, LLDAS was attained by 36.2%, 36.7% and 33.5%, DORIS-remission by 12.3%, 11.6% and 17.8%, and Padua-remission by 21.3%, 17.9% and 29.0%, respectively (attrition-corrected). Trajectory analysis of activity indices classified patients into complete (25.5%), partial (42.0%) and non-responder (32.4%) groups, which were predicted by baseline PGA, inflammatory rash, leukopenia and prior use of mycophenolate. During median follow-up of 15 months, efficacy-related discontinuations occurred in 31.4% of the cohort, especially in patients with higher baseline PGA (hazard ratio [HR] 2.78 per 1-unit; 95% CI 1.32-5.85). Conversely, PGA improvement at 3 months predicted longer drug retention (HR 0.57; 95% CI 0.33-0.97). Use of hydroxychloroquine was associated with lower risk for safety-related drug discontinuation (HR 0.33; 95% CI 0.13-0.85). Although severe flares were reduced, flares were not uncommon (58.0%) and contributed to treatment stops (odds ratio [OR] 1.73 per major flare; 95% CI 1.09-2.75) and damage accrual (OR 1.83 per mild/moderate flare; 95% CI 1.15-2.93).ConclusionsIn a real-life setting with predominant long-standing SLE, belimumab was effective in the majority of patients, facilitating the achievement of therapeutic targets. Monitoring PGA helps to identify patients who will likely benefit and stay on the treatment. Vigilance is required for the prevention and management of flares while on belimumab.

Background:The current goal of treatment in SLE is remission or low disease activity (LDA) and prevention of flares, achieved with the lowest possible dose of glucocorticoids. Nevertheless, in current clinical practice a significant number of patients still has active disease.1,2Objectives:To assess the current disease activity state of SLE patients during their most recent visit in two centers (Department of Rheumatology in “Asklepieio” Hospital and Rheumatology Unit in “Attikon” Hospital, both in Athens, Greece).Methods:Cross-sectional study of patients with a diagnosis of SLE for at least one year. Patients were divided into four groups: 1) Remission off-therapy: SLE Disease Activity Index (SLEDAI)=0 without prednisone or immunosuppressive drugs (IS), 2) Remission on-therapy: SLEDAI=0, prednisone dose ≤5mg/day and/or IS (conventional and biologic, maintenance phase), 3) LDA: SLEDAI ≤4, prednisone dose ≤7.5mg/day and/or IS (maintenance phase), 4) Active disease: SLEDAI >4 and/or prednisone dose >7.5mg/day and/or IS (induction phase).2 Hydroxychloroquine was allowed in all groups.Results:205 patients were included [95.1% female, mean (SD) age 48.4 (14.9) years and median disease duration (IQR) 6.2 (12.6) years]. A history of lupus nephritis and neuropsychiatric SLE was present in 16.6% and 17.1% of our patients, respectively, and 39% of patients had SLICC/ACR damage index (SDI) > 0. At last visit, remission off-therapy and remission on-therapy was present in 8.3% (n=17) and 15.1% (n=31) of our patients, respectively. Seventy-five patients (36.6%) had LDA, whereas 82 patients (40%) had active disease. More than 85% (86.3%) of patients were in treatment with hydroxychloroquine and 64.4% were receiving immunosuppressive drugs. Regarding glucocorticoids, 50.2% (n=103) were treated with prednisone dose ≤7.5mg/day and over 40% (42.4%, n=87) did not receive prednisone at all. A SLEDAI score 0 and 1-4 was achieved in 24.4% and 42.9% of patients, respectively, but only 3.9% had a SLEDAI > 8, indicative of high disease activity.Conclusion:Although the majority of our patients were treated with hydroxychloroquine and glucocorticoids in acceptable levels of daily dose, four out of ten patients in our practice have active disease during their last visit. Achieving treatment goals in SLE patients remains a challenge for future novel therapies.References:[1]Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis 2019; 78: 736–745.[2]Ugarte-Gil MF, Wojdyla D, Pons-Estel GJ, et al. Remission and Low Disease Activity Status (LDAS) protect lupus patients from damage occurrence: data from a multiethnic, multinational Latin American Lupus Cohort (GLADEL). Ann Rheum Dis 2017; 76: 2071–2074.Disclosure of Interests:None declared

Ankylosing spondylitis (AS) is an inflammatory disease affecting mainly the sacroiliac joints and the spine. In long-standing disease, the fused spine of AS patients is susceptible to spinal fractures, even after low impact trauma. We present a 61-year-old man with long-standing AS who presented with anterior and posterior longitudinal ligament rupture and T12 and L1 vertebral endplates fractures (a so called “chalk-stick fracture”) without reporting any prior trauma and discuss relevant issues.

BackgroundLow disease activity is a validated target of systemic lupus erythematosus (SLE) therapy.Objectivesτo assess the ability of belimumab to induce low disease activity states in real-life setting.MethodsMulticentre prospective observational study of SLE patients receiving belimumab due to active disease, refractory to at least one conventional immunosuppressant. Disease activity, including attainment of lupus low disease activity state (LLDAS) and remission-on-glucocorticoids (GC) (clinical SLEDAI-2K=0 with prednisone ≤5 mg/day), accrual of organ damage, flares and side effects were documented.ResultsNinety-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 decreased average SLEDAI-2K, physician global assessment and daily prednisone dose over time, as early as 3 months after initiation. Complete withdrawal of GC was achieved in 17.8%, 22.5%, 31.7% and 23.3% at 3, 6, 9 and 12 months, respectively. The number of flares and severe flares was reduced by 62% and 50%, respectively, during the first year of treatment. Although reduction in clinical SLEDAI-2K was more pronounced in patients who were serologically active (from 8 to 1.5 at 12 months) compared to serologically inactive (from 6 to 4) at baseline, attainment of low disease activity states (LLDAS or remission) did not differ between groups and was reached by more than 40% of completers after 9–12 months (figure 1). Twenty patients (22.0%) discontinued treatment due to inadequate response and two due to side effects potentially related to the drug.ConclusionsBelimumab is efficacious in achieving low disease activity in over 40% of active SLE patients, accompanied by complete GC discontinuation in more than 20%. Serologically active and inactive patients respond equally to the drug.References[1] Franklyn K, et al. Definition and initial validation of a Lupus Low Disease Activity State (LLDAS). Ann Rheum Dis. 2016;75(9):1615–21.[2] Zen M, et al. Prolonged remission in Caucasian patients with SLE: prevalence and outcomes. Ann Rheum Dis. 2015;74(12):2117–22.Disclosure of InterestNone declared

BackgroundData on the efficacy of belimumab in SLE mainly originate from large randomized clinical trials, whereas reports from real-life clinical practice are lacking.ObjectivesTo describe the clinical experience from the use of belimumab in Greece since the approval of the drug.MethodsMulticentre 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.ResultsA 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.ConclusionsIn 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 InterestNone declared

BackgroundBelimumab has been introduced in the management of SLE for more than 10 years, however long-term efficacy and safety data are still limited and mostly derive from the extended phase of randomized clinical trials.ObjectivesTo evaluate the long-term survival of belimumab treatment, reasons for treatment cessation and associated predictors in routine care setting.MethodsMulticentre observational study of adult SLE patients who were treated with belimumab according to physician discretion and in line with the EULAR recommendations. Disease activity (Physician Global Assessment [PGA]: scale 0-3; SLE disease activity index-2000 [S2K]), flares (SELENA-SLEDAI Flare Index), organ damage (SLICC damage index [SDI]), co-administered treatments and dosage, adverse events and causes of belimumab discontinuation were monitored prospectively at 3–6-month intervals. Cox-regression analysis was performed to identify factors associated with reduced drug survival.ResultsA total 184 patients treated with belimumab for at least 3 months were included (women 95.6%; mean ± SD age 48.8 ± 13.4 years; disease duration 9.2 ± 11.3 years). Baseline S2K and PGA were 7.5 ± 3.0 and 1.64 ± 0.42, respectively, both demonstrating significant improvement at 6 months (4.5 ± 3.5 and 1.02 ± 0.69, respectively; p<0.001) and 12 months (3.5 ± 3.1 and 0.68 ± 0.55, respectively; p<0.001). Of patients receiving glucocorticoids at onset, 49.0% tapered the dose and 17.6% completely withdrew them. After a median (interquartile range) follow-up of 15.1 (16.9) months, 44.0% of patients discontinued belimumab due to suboptimal efficacy as judged by the treating physician (28.3%), adverse events (including infections) (9.8%) or other causes (e.g., pregnancy, patient decision). Accordingly, efficacy-related drug survival rates at 1 and 2 years were 70% and 61%, respectively, with corresponding safety-related survival rates of 94% and 87%, respectively. Baseline factors associated with belimumab discontinuation due to suboptimal efficacy included PGA >1.50 (hazard ratio [HR] 3.66; 95% confidence interval [95% CI] 1.14–11.73; p=0.029) and severe (RA-like) arthritis (HR 2.56; 95% CI 1.16–5.68; p=0.020) but not disease duration, use of glucocorticoids, active serology or organ damage. Notably, patients with early (3 months) improvement (i.e., any decrease in PGA) showed significantly lower risk for treatment cessation (HR 0.38; 95% CI 0.22–0.67; p=0.001) (Figure 1) and this effect was independent of the initial PGA level. Baseline use of hydroxychloroquine was associated with prolonged safety-related belimumab survival (HR 0.32; 95% CI 0.12–0.88; p=0.028).Figure 1.Efficacy-related survival of belimumab according to improvement or not of PGA at 3 months since treatment initiation.ConclusionIn real-life setting, about 28% of SLE patients discontinue belimumab due to suboptimal treatment response per physician judgement, especially those with moderate-to-high activity and severe arthritis. Improvement in PGA at 3 months predicts long-term drug maintenance, therefore suggesting its value for patient monitoring. Our data confirm the very good tolerability of belimumab and identify hydroxychloroquine co-administration as a predictor for prolonged safety-related drug survival.AcknowledgementsThe study was partly funded by the Greek Rheumatology Society and the Greek Association of Professional Rheumatologists (ERE-EPERE) and by Pfizer Global Medical GrantsDisclosure of InterestsMyrto Nikoloudaki: None declared, Dionysis Nikolopoulos: None declared, SOFIA KOUTSOVITI: None declared, Irini Flouri: None declared, Noemin Kapsala: None declared, ARGYRO REPA: None declared, PELAGIA KATSIMPRI: None declared, EVANGELOS THEOTIKOS: None declared, Sofia Pitsigavdaki: None declared, Katerina Pateromichelaki: None declared, Anastasios Eskitzis: None declared, ANTONIA ELEZOGLOU: None declared, Prodromos Sidiropoulos: None declared, Antonis Fanouriakis: None declared, Dimitrios Boumpas: None declared, George Bertsias Speakers bureau: GSK, AstraZeneca, Pfizer, SOBI, UCB, Novartis, AENORASIS, Abbvie, Grant/research support from: GSK, Pfizer