Maddalena Larosa

Effects of Belimumab on Flare Rate and Expected Damage Progression in Patients With Active Systemic Lupus Erythematosus

To investigate effectiveness and safety of belimumab in patients with active systemic lupus erythematosus (SLE) in a clinical practice setting.

Belimumab decreases flare rate and hinders the expected damage progression in patients with active systemic lupus erythematosus.

To investigate effectiveness and safety of belimumab in patients with active systemic lupus erythematosus (SLE) in a clinical practice setting.

Cardiovascular risk factors, burden of disease and preventive strategies in patients with systemic lupus erythematosus: a literature review.

Introduction: Risk of developing cardiovascular disease (CVD) is increased in systemic lupus erythematosus (SLE) compared with the general population. Traditional risk factors cannot account for the totality of CV events and adequate prevention may be challenging. Areas covered: This review summarizes traditional and emerging risk factors of CVD in SLE patients and goes over potential pathogenic mechanisms involved in CVD development. Role of commonly used drugs and preventive strategies exploitable in everyday clinical practice are also discussed. Expert opinion: SLE-related risk factors involve both disease- and treatment-related features, including disease activity, disease phenotype, corticosteroid misuse and alterations of innate and adaptive immunity. Primary prevention is mandatory in management of lupus patients through appropriate disease control, corticosteroid tapering, use of antimalarials and eventually vitamin D supplementation.

Advances in the diagnosis and classification of systemic lupus erythematosus

ABSTRACT Introduction: Systemic lupus erythematosus (SLE) is the prototype of systemic autoimmune diseases. Patients with SLE display a wide spectrum of clinical and serological findings that can mislead and delay the diagnosis. Diagnostic criteria have not been developed yet, whereas several sets of classification criteria are available; however, none of them has 100% sensitivity and 100% specificity, i.e. the hallmark of diagnostic criteria. Nevertheless, classification criteria are often misused as diagnostic criteria, which may affect earliness of diagnosis and lead to more misdiagnosed cases. Areas covered: In this review, we compare old and new classification criteria, discussing their application and pinpointing their limitations in the management of patients. Moreover, we will focus on current and novel biomarkers for SLE diagnosis, highlighting their predictive value and applicability in clinical practice. Expert commentary: SLE diagnosis still represents a challenge, remaining largely based on a clinical judgment. Besides SLE diagnosis, even its classification is still challenging to date. Indeed, although classification of SLE seems to be achieved more frequently with the 2012 SLICC criteria than with the previous 1997 ACR criteria, this last-updated 2012 set might be improved. Notably, diagnostic and classification criteria should be applied to any subject in the world, and consequently they should include immunological variables validated in different populations, which is still an unmet need.

Lupus low disease activity state is associated with a decrease in damage progression in Caucasian patients with SLE, but overlaps with remission

Objective To evaluate the prevalence, duration and effect on damage accrual of the ‘Lupus Low Disease Activity State’ (LLDAS) in a monocentric cohort of patients with systemic lupus erythematosus (SLE). Methods We studied 293 Caucasian patients with SLE during a 7-year follow-up period. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and SELENA-SLEDAI physician global assessment (PGA), and damage by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We considered the following definition of LLDAS: SLEDAI-2K ≤4 without major organ activity, no new disease activity, PGA (0–3)≤1, prednisone ≤7.5 mg/day and well-tolerated immunosuppressant dosages. The effect of LLDAS on SDI was evaluated by multivariate regression analysis. We also evaluated remission defined as clinical SLEDAI-2K=0 and prednisone ≤5 mg/day in patients treated with/without stable immunosuppressants and/or antimalarials. Results LLDAS lasting 1, 2, 3, 4 or ≥5 consecutive years was achieved by 33 (11.3%), 43 (14.7%), 39 (13.3%), 31 (10.6%) and 109 (37.2%) patients, respectively. Patients who spent at least two consecutive years in LLDAS had significantly less damage accrual compared with patients never in LLDAS (p=0.001), and they were significantly less likely to have an increase in SDI (OR 0.160, 95% CI 0.060 to 0.426, p<0.001). On average, 84% of patients in LLDAS also fulfilled the criteria for remission. Conclusions LLDAS was associated with a decrease in damage progression in Caucasian patients with SLE. The majority of patients in LLDAS were in remission, which can largely contribute to the protective effect of LLDAS on damage accrual.

Can we manage lupus nephritis without chronic corticosteroids administration

The outcome of lupus nephritis (LN) has changed since the introduction of glucocorticoids (GCs), which dramatically reduced the mortality related to one of the most severe complications of systemic lupus erythematosus (SLE). Since the 1950s, other immunosuppressants, including biologic drugs (i.e. rituximab) have aided in maintaining remission, preserving kidney function, but not preventing treatment-related toxicity. GCs still remain the cornerstone in the treatment of SLE, including LN, and they are widely used in clinical practice. However, GC administration represents a double-edged sword. Indeed, from one side they allow a fast and effective control of disease activity by dampening inflammation; from the other side, they have many and severe side effects leading to organ damage. In this paper, we will discuss pros and cons of the chronic use of GCs, especially focusing on LN.

S1D:4 Testing different definitions of remission in a monocentric caucasian cohort of sle patients

Objective To evaluate the prevalence of different definitions of remission and their effect on damage in systemic lupus erythematosus (SLE). Design and method We considered 293 caucasian SLE patients followed-up for 7 years (2009–2015): 253 (86.3%) were female, mean ±SD disease duration 11.1±7.8 years. Disease activity was assessed by clinical SLEDAI-2K (c-SLEDAI) and damage by SLICC/ACR Damage Index (SDI). We evaluate the effect of different definitions of remission (c-SLEDAI=0; c-SLEDAI ≤1; c-SLEDAI=0 and prednisone ≤5 mg/day; c-SLEDAI ≤1 and prednisone ≤5 mg/day; c-SLEDAI=0 and PGA <0.5; c-SLEDAI ≤1 and PGA <0.5; c-SLEDA I=0 and prednisone ≤5 mg/day and PGA <0.5; c-SLEDAI ≤1 and prednisone ≤5 mg/day and PGA <0.5) and different durations of remission (1, 2, 3, 4, ≥5 consecutive years) on SDI using multiple logistic regression analysis. Results Frequency of remission achieved during the 7 year follow-up are reported in table 1 according to the different definitions. The mean increase in SDI and the percentage of patients with increased of SDI from the baseline to the end of follow-up were significantly higher in unremitted and 1 year remitted patients compared with patients with 2-, 3-, 4- and ≥5 year remission, irrespective of the definition of remission. 5 year remitted patients had lower damage compared with 2 year (p<0.01) and 3 year (p<0.01) remitted patients. At multivariate analysis, a remission lasting at least 2 years was an independent predictor of no damage accrual only in the definitions including prednisone intake ≤5 mg/day and/or PGA <0.5 (table 2). Conclusions The inclusion of PGA <0.5 in the definition reduces the frequency of remission only in the long-term (≥5 year). A sustained remission, regardless of its definition, is associated with a lower chronic damage development. The addition of prednisone ≤5 mg/day and/or PGA <0.5 to c-SLEDAI=0/≤1 increases the ability to predict the absence of damage accrual compared with cSLEDAI=0/≤1 without substantial differences among them.Abstract S1D:4 Table 1 Proportion of patients achieving different levels of remission according to the duration of remissionAbstract S1D:4 Table 2 Multivariate analysis: predictors of damage accrual over the follow-up

Therapy of scleroderma renal crisis: State of the art

Scleroderma renal crisis (SRC) is an uncommon but still life-threatening manifestation of systemic sclerosis (SSc). The incidence of SRC has decreased in the last few decades, probably due to a widespread use of vasodilators in SSc patients. It is well-recognized that exposure to different drugs can trigger SRC (corticosteroids, cyclosporine) or might prevent its occurrence (iloprost, calcium channel blockers). The prognosis of this life-threatening manifestation has not substantially improved since 1980s, when ACE-inhibitors were introduced in its treatment. ACE-inhibitors remain the mainstay in the therapy of SRC due to their efficacy in controlling malignant hypertension; indeed, the prognosis largely depends on the rapid improvement of the ongoing renal ischemia. Calcium-channel blockers and in third line diuretics and alpha-blockers should be used as additional therapy if blood pressure control remains suboptimal despite maximum tolerated doses of ACE-inhibitors. Given the growing evidence on the role of complement activation and endothelin-1 in the pathogenesis of SRC, recent case-series and case reports have suggested the use of C5-inhibitors and endothelin receptor antagonists in the therapy of SRC, mainly in the refractory cases. Plasma-exchange seems to give some benefits in patients with SRC and microangiopathy or intolerant to ACE-inhibitors. Renal transplantation is the last treatment option and its outcome is similar to that reported in other connective tissue disorders, with a 5-year patient survival rate of about 82%. In this review we summarize the current knowledge in the treatment of SRC.

95 Efficacy, damage accrual and predictors of response to belimumab in active sle patients: a large italian multicenter prospective study

Background and aims To investigate effectiveness, damage accrual and predictors of response to belimumab in active SLE patients in clinical practice setting. Methods 188 active SLE patients with anti-dsDNA antibodies and low C3 and/or C4, from 11 Italian centres, were treated with belimumab as add-on-therapy. Gender, age, disease duration, polyarthritis, skin rashes, glomerulonephritis, haematological involvement, SLEDAI-2K≥10, prednisone ≥7,5 mg/day and concomitant immunosuppressants were used to determine baseline predictors of 12- and 24 month response according to SRI-4. Data were analysed by SPSS (version 22.0). Results Prominent clinical manifestations are summarised in Table 1. Clinical and serological variables at baseline, 12 and 24 months are reported in Table 2. SRI-4 was achieved by 71.3% and 68.7% of patients at 12 and 24 months, respectively. 92% of 12 month responders maintained SRI-4 response at 24 months; conversely, 87.5% of non-responders at 12 months were non-responders even at 24 months. Drug discontinuation for any cause was observed in 36.2% of patients; median treatment duration was 12 months. Damage accrual variation was significant between 5 years before drug initiation and baseline (p<0.001), but not between baseline and the end of follow-up (p=0.083). Baseline predictors of 12 month response were SLEDAI-2K≥10 (OR 25.8, 4.19–159.2) and polyarthritis (OR 8.33, 1.88–36.78); 24 month response predictors were SLEDAI-2K≥10 (OR 12.11, 1.63–89.80), polyarthritis (OR 32.56, 2.94–360.56), and prednisone dose ≥7.5 mg/day (OR 7.88, 1.02–61.48). Table 1 Refractory prominent clinical manifestation at baseline. Table 2 Disease features at baseline, 12 and 24 months (mean±SD). Conclusions Belimumab seems to be effective and to reduce damage accrual in SLE patients in clinical practice setting. Patients with arthritis and high disease activity were the best responders to belimumab.

404 Predictors of renal remission, renal insufficiency and damage in lupus nephritis

Background and aims To explore predictors of renal remission, insufficiency and damage in lupus nephritis (LN). Methods We retrospectively analysed our lupus cohort and studied LN patients with at least one renal biopsy since 1990 until 2016. Follow-up ended at last patient visit. Complete renal remission (CRR) was defined as proteinuria <0.5 g/day and normal serum creatinine (SCr); partial remission as proteinuria <3.5 g/day with normal SCr; renal failure as SCr ≥2 mg/dl; renal flare as an increase in proteinuria >0.5 g/day and/or requirement for treatment modifications. Damage was measured by SLICC damage index (SDI). Results 81 patients were studied (Table) who underwent 110 biopies. Forty patients (49.3%) went into CRR by the end of follow-up. Thirty-six (44.5%) had 2 renal flares while 21≥3 (26%). Six patients developed renal failure preceded by ≥3 flares in 5. One case of ESRD was reported. By the end of follow-up 30 patients (37%) had SDI≥2. At univariate analysis, increased proteinuria at 12 and 24 months from first biopsy and higher flare number were inversely associated with CRR, while long-lasting hypertension, abnormal SCr, decreased GFR and C4 at time of first biopsy were associated with renal failure. At multivariate analysis 24h-proteinuria at 24 months independently predicted lack of CRR (OR 3.7), while a higher number of renal flares (OR 5.27), higher SCr at 6 months from renal biopsy (OR 5.01) and a longer disease duration (OR 6.34) were independently associated with damage accrual. Conclusions Increased proteinuria and abnormal baseline renal function make CRR unlikely. Suboptimal control of LN activity and longer disease duration are associated with severe damage accrual.