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.
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.
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
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