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1.
Artigo em Inglês | MEDLINE | ID: mdl-33547784

RESUMO

OBJECTIVES: Atacicept reduced SLE disease activity in the Phase IIb ADDRESS II study, particularly in patients with high disease activity (HDA; SLEDAI-2K ≥10) at screening. We assessed long-term safety and efficacy of atacicept in the long-term extension (LTE) of ADDRESS II. METHODS: In the 24-week, randomised, double-blind, placebo-controlled ADDRESS II study, patients received weekly atacicept (75 or 150 mg) or placebo. Atacicept was continued at the same dose in atacicept-treated patients in the LTE; placebo-treated patients switched to atacicept 150 mg. Long-term safety was the primary end point. Secondary endpoints included SLE responder index (SRI)-4 and SRI-6 response rates and flares. RESULTS: 253 patients entered the ADDRESS II LTE; 88 received atacicept 150 mg, 82 atacicept 75 mg and 83 placebo/atacicept 150 mg. Median active treatment duration in the LTE was 83.8 weeks. Frequencies of treatment-emergent adverse events (TEAEs) were similar across groups (90.4-93.2%). 12.5%, 14.6% and 21.7% of patients in the atacicept 150 mg, atacicept 75 mg and placebo/atacicept 150 mg groups reported serious TEAEs during the treatment period. The proportions of patients with TEAEs leading to discontinuation were 5.7%, 4.9% and 10.8%, respectively. SRI-4 and SRI-6 response rates were maintained with atacicept in the modified intent-to-treat and HDA populations and those on continuous 150 mg had a reduced risk of first severe flare and longer time to first severe flare vs those who initially received placebo. CONCLUSION: Long-term treatment with atacicept 150 mg in SLE patients had an acceptable safety profile, with durable efficacy. CLINICAL TRIAL REGISTRATION NUMBER: NCT02070978.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33555325

RESUMO

OBJECTIVES: Vitamin D (25(OH)D) deficiency and metabolic syndrome (MetS) may both contribute to increased cardiovascular risk in systemic lupus erythematosus (SLE). We aimed to examine the association of demographic factors, SLE phenotype, therapy and vitamin D levels with MetS and insulin resistance. METHODS: The Systemic Lupus International Collaborating Clinics (SLICC) enrolled patients recently diagnosed with SLE (<15 months) from 33 centres across 11 countries from 2000. Clinical, laboratory and therapeutic data were collected. Vitamin D level was defined according to tertiles based on distribution across this cohort, which were set at T1 (10-36 nmol/l), T2 (37-60 nmol/l) and T3 (61-174 nmol/l). MetS was defined according to the 2009 consensus statement from the International Diabetes Federation. Insulin resistance was determined using the HOMA-IR model. Linear and logistic regressions were used to assess the association of variables with vitamin D levels. RESULTS: Of the 1847 patients, 1163 (63%) had vitamin D measured and 398 (34.2%) subjects were in the lowest 25(OH)D tertile. MetS was present in 286 of 860 (33%) patients whose status could be determined. Patients with lower 25(OH)D were more likely to have MetS and higher HOMA-IR. The MetS components, hypertension, hypertriglyceridemia and decreased HDL were all significantly associated with lower 25(OH)D. Increased average glucocorticoid exposure was associated with higher insulin resistance. CONCLUSIONS: MetS and insulin resistance are associated with lower vitamin D in patients with SLE. Further studies could determine whether vitamin D repletion confers better control of these cardiovascular risk factors and improve long-term outcomes in SLE.

3.
Thromb Res ; 198: 213-221, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33485122

RESUMO

Thrombotic antiphospholipid syndrome (APS) is characterised by venous, arterial and/or small vessel thrombosis in the context of persistently positive antiphospholipid antibodies (aPL). The diagnosis and management of thrombotic APS continues to prove challenging for clinicians. We provide a practical guide to the diagnosis of APS including who to test for aPL and which tests to do. We also consider clinical practice points on the management of venous, arterial and small vessel thrombosis, in the context of first and recurrent thrombotic events. Non-criteria manifestations of APS are reviewed. An approach to recurrent thrombosis and anticoagulant-refractory APS is discussed, with options including increasing the anticoagulation intensity of vitamin K antagonists, switching to low-molecular-weight-heparin, the use of fondaparinux and/or the addition of antiplatelet treatment. Adjunctive options such as vitamin D, hydroxychloroquine and statins are also addressed.

4.
Lupus ; : 961203320982668, 2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33459161

RESUMO

It is now two decades since Rituximab was first used in the treatment of patients with systemic lupus erythematosus. There have been many challenges but in spite of failing to meet its primary endpoints in two clinical trials it is widely used for many aspects of lupus, its side-effects and the possibility that combining it with Benlysta may be of value. We also consider the proposal that it may provide a useful initial therapy. In this review, we consider the place of Rituximab in the treatment of lupus and anticipate how developments in fully-humanized anti-CD20 monoclonals may well extend the "therapeutic life" of B-cell depletion as a viable treatment option.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33493333

RESUMO

OBJECTIVES: To characterize the phenotypic presentation at diagnosis of childhood-onset primary Sjögren syndrome (SjS). METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry using worldwide data-sharing cooperative merging of pre-existing clinical SjS databases from the five continents. For this study, we selected those patients in whom the disease was diagnosed below the age of 19 according to the fulfilment of the 2002/2016 classification criteria. RESULTS: Among the 12 083 patients included in the Sjögren Big Data Registry, 158 (1.3%) patients had a childhood-onset diagnosis (136 girls, mean age of 14.2 years): 126 (80%) reported dry mouth, 111 (70%) dry eyes, 52 (33%) parotid enlargement, 118/122 (97%) positive minor salivary gland biopsy and 60/64 (94%) abnormal salivary ultrasound study, 140/155 (90%) positive antinuclear antibody, 138/156 (89%) anti-Ro/La antibodies and 86/142 (68%) positive rheumatoid factor. The systemic ESSDAI domains containing the highest frequencies of active patients included the glandular (47%), articular (26%) and lymphadenopathy (25%) domains. Patients with childhood-onset primary SjS showed the highest mean ESSDAI score and the highest frequencies of systemic disease in 5 (constitutional, lymphadenopathy, glandular, cutaneous and haematological) of the 12 ESSDAI domains, and the lowest frequencies in 4 (articular, pulmonary, peripheral nerve and central nervous system) in comparison with patients with adult-onset disease. CONCLUSIONS: Childhood-onset primary SjS involves around 1% of patients with primary SjS, with a clinical phenotype dominated by sicca features, parotid enlargement and systemic disease. Age at diagnosis plays a key role on modulating the phenotypic expression of the disease.

6.
Lupus ; : 961203320988607, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472522

RESUMO

BACKGROUND: Systemic Lupus Erythematosus (SLE) an autoimmune rheumatic disease with a complex pathogenesis, remains potentially life-threatening. SLE patients have increased morbidity and premature mortality compared to non-SLE patients. The five-year survival rate has improved from <50% in the 1950s to >90% in the 1980s. Lupus patients still have a mortality risk three times that of the general population. OBJECTIVES: To provide a detailed analysis of the causes of death, main characteristics and trends in the management of the deceased SLE patients from the lupus clinic at the University College London Hospital (UCLH); during the past four decades. METHODS: This was a non-interventional, retrospective study based on historical real-world data from paper and electronic records of patients followed up at UCLH. The analysis focused on data collected between 1st January 1978 and 31th December 2018. We collected the: causes of death, duration of disease, key laboratory and clinical parameters and the treatment received. We compared the results from the four decades to ascertain trends in the causes of mortality. All statistical analyses were performed using the Statistical Package for Social Sciences (SPSS), version 22.0. The 95% confidence intervals for the means of data were calculated. RESULTS: 111 SLE patients (15%), died during follow-up. Their median age was 51 years (interquartile range (IQR) = 38-63 years) and the median duration of disease, 15 years (IQR = 8.5-24 years). The main causes of death in the past 40 years were infection (31.7%), cancer (26.7%) and cardiovascular disease (CVD) (21.8%). 93.6% of these patients were immunosupressed. During the 40-year period, there were several therapeutic developments notably the introduction of mycophenolate mofetil (MMF) and rituximab; the latter initially only given to patients when more conventional inmunosupressants had failed, but more recently offered to patients at diagnosis. There was a statistically significant increase in the use of hydroxycloroquine (HCQ), MMF and rituximab. In contrast, the use of Azathioprine (AZA) and steroids, hardly changed over time. CONCLUSIONS: This retrospective review shows how epidemiological factors, causes of death and treatment of SLE patients have changed during the last 40 years in the UCLH cohort.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33404639

RESUMO

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) have an increased risk of developing cardiovascular disease (CVD). Multiple studies have shown that these patients have increased numbers of carotid plaques and greater intima-media thickness (IMT) than healthy controls. Measures such as total plaque area (TPA) and plaque echogenicity may be more sensitive and more relevant to cardiovascular risk than presence of plaque and IMT alone. Our objective was to produce the first report of TPA and echogenicity in a population of. PATIENT: s with SLE. METHODS: One hundred patients with SLE and no history of clinical CVD were recruited. Clinical, serological and treatment variables were recorded and serum was tested for antibodies to apolipoprotein A-1 and high-density lipoprotein. Both carotid and both femoral artery bifurcations of each patient were scanned to determine IMT, TPA and echogenicity of plaques. Univariable and multivariable statistical analyses were carried out to define factors associated with each of these outcomes. RESULTS: Thirty-six patients had carotid and/or femoral plaque. Increasing age was associated with presence of plaque and increased IMT. Triglyceride levels were associated with presence of plaque. Mean (SD) TPA was 60.8 (41. 6) mm2. Patients taking prednisolone had higher TPA. Most plaques were echolucent but increased echogenicity was associated with prednisolone therapy and persistent disease activity. CONCLUSION: TPA and plaque echogenicity in patients with SLE are associated with different factors than those associated with presence of plaque and IMT. Longitudinal studies may show whether these outcome measures add value in the management of cardiovascular risk in SLE.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33221918

RESUMO

OBJECTIVES: Chronic glucocorticoid use is complicated by osteoporosis and increases the risk of fragility fractures. EULAR guidelines on SLE management recommend reducing chronic glucocorticoid dosage to ≤7.5 mg/day to minimize this risk. We examined the relationship of glucocorticoid dose to fragility fracture risk in a cohort of SLE patients. METHODS: Retrospective analysis of SLE patients attending University College Hospital over 28 years was undertaken. Collected data included consecutive steroid dose, dual-energy X-ray absorptiometry scans and fragility fractures. RESULTS: We collected data on 250 patients with a median of 17 years' follow-up. Fragility fractures were diagnosed in 28 (11.2%) patients and the mean ± s.d. age of first fracture was 51 ± 16 years. A total of 94% received glucocorticoids, the average dose being 6.20 mg/day. Patients with fragility fractures had a lower average daily dose (5.36 vs 6.23 mg/day) but a higher median cumulative dose (25.19 vs 20.96 g). These differences were not significant (P = 0.127 and 0.229, respectively). Some 93% of patients received vitamin D, and 85% received calcium. Cox regression analysis showed older age at SLE diagnosis, osteoporosis and secondary hyperparathyroidism were associated with fragility fractures. Glucocorticoid dose was not significantly associated with the occurrence of fragility fractures. Twenty-two patients with fractures were treated with bisphosphonates, two with denosumab and two with teriparatide. CONCLUSIONS: We found no significant association between glucocorticoid treatment and fragility fractures in our group of patients; however, a prospective study including more patients not treated with CS would be necessary to confirm these results.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33216641

RESUMO

INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease characterized by multiple pathologies in which sustained inflammatory activity leads to progressive tissue destruction and organ damage. One of the main proinflammatory cytokines playing a key role in autoimmune diseases such as rheumatoid arthritis (RA) or SLE, is tumor necrosis factor (TNF) alpha. AREAS COVERED: The introduction of TNF-alpha inhibitors revolutionized the treatment of RA and other conditions including psoriatic arthritis and ankylosing spodylitis. We review here the efficacy and safety of TNF-alpha blockers in SLE focussing on why it has not been more widely used since TNF-alpha was reported to be increased in SLE patients and to correlate with disease activity. EXPERT OPINION: We summarize the reported SLE cases that have received TNF-alpha blockers and the main results to date. We reflect on whether there is a case to reconsider the use TNF-alpha blockade in SLE.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33152181

RESUMO

OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) predicts mortality and damage accrual in SLE, but its association with hospitalizations has not been described. We estimated the association of baseline SLICC-FI values with future hospitalizations in the SLICC inception cohort. METHODS: Baseline SLICC-FI scores were calculated. The number and duration of inpatient hospitalizations during follow-up were recorded. Negative binomial regression was used to estimate the association between baseline SLICC-FI values and the rate of hospitalizations per patient-year of follow-up. Linear regression was used to estimate the association of baseline SLICC-FI scores with the proportion of follow-up time spent in hospital. Multivariable models were adjusted for relevant baseline characteristics. RESULTS: The 1549 SLE patients eligible for this analysis were mostly female (88.7%) with mean (SD) age 35.7 (13.3) years and median (IQR) disease duration 1.2 (0.9-1.5) years at baseline. Mean (SD) baseline SLICC-FI was 0.17 (0.08). During mean (SD) follow-up of 7.2 (3.7) years, 614 patients (39.6%) experienced 1570 hospitalizations. Higher baseline SLICC-FI values (per 0.05 increment) were associated with more frequent hospitalizations during follow-up (Incidence Rate Ratio 1.21; 95%CI 1.13-1.30), adjusting for baseline age, sex, corticosteroid use, immunosuppressive use, ethnicity/location, SLE disease activity index 2000 (SLEDAI-2K), SLICC/ACR damage index (SDI), and disease duration. Among patients with ≥1 hospitalization, higher baseline SLICC-FI values predicted a greater proportion of follow-up time spent hospitalized (Relative Rate 1.09; 95%CI 1.02-1.16). CONCLUSION: The SLICC-FI predicts future hospitalizations among incident SLE patients, further supporting the SLICC-FI as a valid health measure in SLE.

13.
Nat Rev Rheumatol ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33139947

RESUMO

The emergence of COVID-19 in early 2020 led to unprecedented changes to rheumatology clinical practice worldwide, including the closure of research laboratories, the restructuring of hospitals and the rapid transition to virtual care. As governments sought to slow and contain the spread of the disease, rheumatologists were presented with the difficult task of managing risks, to their patients as well as to themselves, while learning and implementing new systems for remote health care. Consequently, the COVID-19 pandemic led to a transformation in health infrastructures and telemedicine that could become powerful tools for rheumatologists, despite having some limitations. In this Viewpoint, five experts from different regions discuss their experiences of the pandemic, including the most challenging aspects of this unexpected transition, the advantages and limitations of virtual visits, and potential opportunities going forward.

14.
Clin Exp Rheumatol ; 38 Suppl 126(4): 85-94, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33095152

RESUMO

OBJECTIVES: To evaluate the systemic phenotype associated with the presence of isolated anti-La/SSB antibodies in a large international registry of patients with primary Sjögren's syndrome (pSS) fulfilling the 2002 classification criteria. METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. Baseline clinical information from leading centres on clinical research in SS of the 5 continents was collected. Combination patterns of anti-Ro/SSA-La/SSB antibodies at the time of diagnosis defined the following four immunological phenotypes: double positive (combined Ro/SSA and La/SSB,) isolated anti-Ro/SSA, isolated anti-La/SSB, and immunonegative. RESULTS: The cohort included 12,084 patients (11,293 females, mean 52.4 years) with recorded ESSDAI scores available. Among them, 279 (2.3%) had isolated anti-La/SSB antibodies. The mean total ESSDAI score at diagnosis of patients with pSS carrying isolated anti-La/SSB was 6.0, and 80.4% of patients had systemic activity (global ESSDAI score ≥1) at diagnosis. The domains with the highest frequency of active patients were the biological (42.8%), glandular (36.8%) and articular (31.2%) domains. Patients with isolated anti-La/SSB showed a higher frequency of active patients in all ESSDAI domains but two (articular and peripheral nerve) in comparison with immune-negative patients, and even a higher absolute frequency in six clinical ESSDAI domains in comparison with patients with isolated anti-Ro/SSA. In addition, patients with isolated anti-La/SSB showed a higher frequency of active patients in two ESSDAI domains (pulmonary and glandular) with respect to the most active immunological subset (double-positive antibodies). Meanwhile, systemic activity detected in patients with isolated anti-La/SSB was overwhelmingly low. Even in ESSDAI domains where patients with isolated anti-La/SSB had the highest frequencies of systemic activity (lymphadenopathy and muscular), the percentage of patients with moderate or high activity was lower in comparison with the combined Ro/SSA and La/SSB group. CONCLUSIONS: Patients carrying isolated La/SSB antibodies represent a very small subset of patients with a systemic SS phenotype characterised by a significant frequency of active patients in most clinical ESSDAI domains but with a relative low frequency of the highest severe organ-specific involvements. Primary SS still remains the best clinical diagnosis for this subset of patients.


Assuntos
Síndrome de Sjogren , Estudos de Coortes , Feminino , Humanos , Fenótipo , Sistema de Registros , Síndrome de Sjogren/diagnóstico
15.
Lupus ; 29(12): 1571-1593, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33100166

RESUMO

Antiphospholipid syndrome (APS), an acquired autoimmune thrombophilia, is characterised by thrombosis and/or pregnancy morbidity in association with persistent antiphospholipid antibodies. The 16th International Congress on Antiphospholipid Antibodies Task Force on APS Treatment Trends reviewed the current status with regard to existing and novel treatment trends for APS, which is the focus of this Task Force report. The report addresses current treatments and developments since the last report, on the use of direct oral anticoagulants in patients with APS, antiplatelet agents, adjunctive therapies (hydroxychloroquine, statins and vitamin D), targeted treatment including rituximab, belimumab, and anti-TNF agents, complement inhibition and drugs based on peptides of beta-2-glycoprotein I. In addition, the report summarises potential new players, including coenzyme Q10, adenosine receptor agonists and adenosine potentiation. In each case, the report provides recommendations for clinicians, based on the current state of the art, and suggests a clinical research agenda. The initiation and development of appropriate clinical studies requires a focus on devising suitable outcome measures, including a disease activity index, an optimal damage index, and a specific quality of life index.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33111137

RESUMO

OBJECTIVES: To characterize a LN cohort over 40 years, assessing its evolution, analysing two major outcomes: the development of end-stage renal disease and mortality rates in the first 5 years after LN diagnosis. METHODS: An observational retrospective study of patients with LN, followed up from 1975 at University College Hospital. Patients were divided into four groups, depending on the decade of LN diagnosis: 1975-1985 (D1), 1986-1995 (D2), 1996-2005 (D3) and 2006-2015 (D4). Comparison between groups was performed with respect to demographic, clinical, serological and histological characteristics and outcome. RESULTS: Two hundred and nineteen patients with LN were studied. There was a change in ethnic distribution, with a decreasing proportion of Caucasians (58.6% in D1 to 31.3% in D4, P = 0.018) and increase in African-ancestry (17.2% in D1 to 39.6% in D4, P = 0.040). Serological and histological patterns changed throughout time, with a reduction in class IV nephritis (51.7% in D1 to 27.1% in D4, P = 0.035), and increase in class II nephritis (10% in D2 to 18.8% in D4, P = 0.01) and anti-extractable nuclear antigen antibody positivity (17.2% in D1 to 83.3% in D4, P = 0.0001). The 5-year mortality rates decreased from D1 (24.1%) to D2 (4%), stabilizing for the next 30 years. The 5-year progression to end-stage renal disease remained stable over the decades. CONCLUSION: Despite the changes in treatment of LN in the past 20 years, we have reached a plateau in 5-year mortality and progression to end-stage renal disease rates, suggesting that new therapeutic and management approaches, and strategies to enhance adherence, are needed to improve outcomes further in LN patients.

18.
Expert Opin Biol Ther ; : 1-10, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33085537

RESUMO

INTRODUCTION: The type 1 interferon pathway is known to play a role in the immunopathology of systemic lupus erythematosus (SLE). As a result, biologic agents targeting this pathway have been developed and are currently being investigated in clinical trials. AREAS COVERED: We review the biologic agents which have been developed to antagonize type I interferons in SLE. We focus on anifrolumab, a type I interferon receptor antagonist, and consider the complexities of defining efficacy in SLE clinical trials. EXPERT OPINION: Anifrolumab shows promise as an addition to the SLE therapeutic armamentarium. Despite discordant results between its two phase III studies, there is a convincing suggestion of benefit in both trials to encourage the view that this approach might be effective. Data acquired thus far look particularly useful for cutaneous disease. We await data on its effect on renal, pulmonary, cardiac, and central nervous system involvement, on patient reported outcomes, and its safety and efficacy with long-term use.

19.
Blood ; 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32898856

RESUMO

The standard treatment of thrombotic antiphospholipid syndrome (APS) is lifelong oral anticoagulation with a vitamin K antagonist (VKA), generally warfarin. A minority of APS patients re-thrombose despite seemingly adequate anticoagulation. These patients are deemed anticoagulant-refractory. The management of anticoagulant-refractory APS is largely empirical and extrapolated from other clinically similar situations. Further options include increased VKA anticoagulation intensity or alternative antithrombotic strategies, including low-molecular-weight heparin, fondaparinux, the addition of antiplatelet therapy and consideration of vascular options. Anticoagulant-refractory thrombotic APS patients may have APS-associated thrombocytopenia, which necessitates balancing the risk of recurrent thrombosis versus bleeding, to achieve adequate anticoagulation. The multiple mechanisms involved in the generation of the thrombotic phenotype in APS suggest that anticoagulation alone may not control thrombosis. Thus, other modalities, including adjunctive treatment (hydroxychloroquine, statins and vitamin D) for APS-related thrombosis merit consideration, as well as immunomodulatory therapy and complement inhibition. APS patients may have coexistent systemic lupus erythematosus, which adds to the complexity of managing their thromboembolic disease. However, with attention to detail and judicious application of the limited data, it is possible to minimise the morbidity resulting from anticoagulant-refractory thrombotic APS. Multicentre studies are required to guide the sequence of interventions and their comparative efficacy in patients with anticoagulant-refractory thrombotic APS.

20.
Curr Opin Rheumatol ; 32(6): 597-608, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32890026

RESUMO

PURPOSE OF REVIEW: Conventional approaches using hydroxychloroquine, corticosteroids and immunosuppressives have improved the prognosis for systemic lupus erythematosus (SLE) patients. Unfortunately, they have reached the limits of what they can achieve and patients still die prematurely and/or find their quality of life greatly impaired. Here, we discuss the problems of assessing activity in SLE, optimizing clinical trial design and more recent biologic approaches. RECENT FINDINGS: The success of B-cell depletion using Rituximab in open clinical studies, the approval of Belimumab (blocks the B-cell activating factor BAFF) and improvements in clinical trial design, gives cause for hope. Approaches including the use of fully humanized anti-CD20 and CD19 monoclonals, blocking interferons, inhibiting Bruton's tyrosine kinase (BTK), blocking the CD40 ligand (CD40L), utilizing an analogue of the Fc[Latin Small Letter Gamma]RIIB and an IL12-23 blocker and targeting the JAK-STAT pathway have met end points in phase II and III trials. SUMMARY: For 20 years, we hoped that the successes of the biologic therapies in rheumatoid arthritis and psoriatic arthritis would be replicated in SLE but we have been generally disappointed. However, the encouraging recent results with monoclonals that block interferon and fully humanized anti-CD20 in particular, offer the prospect of a real revolution in the treatment of SLE.

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