Íñigo Rúa-Figueroa

Efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus: A systematic review

OBJECTIVE To analyse the efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus (SLE). METHODS We systematically searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials up to June 2013. The following were the selection criteria: (1) adult patients with SLE, (2) rituximab treatment, (3) placebo or active comparator, (4) outcome measures assessing efficacy and/or (5) safety. Meta-analysis, systematic literature reviews, randomised control trials (RCT), open clinical trials and cohort studies were included. Independent extraction of articles by 2 authors using predefined data fields was performed. The quality of each study was graded using the Oxford Levels of Evidence and Jadads scale. RESULTS A total of 26 articles met our inclusion criteria: one RCT and its exploratory analysis, 2 open studies and 22 cohort studies, which analysed 1,231 patients. Overall, patients had active disease refractory to steroids and/or immunosuppressant drugs. Acceptable evidence suggested improvements in disease activity, arthritis, thrombocytopaenia, complement and anti-dsDNA, with a steroid-sparing effect. But relapses of disease were demonstrated too. Weak evidence suggested a response in anaemia, cutaneous and neuropsychiatric manifestations. Available evidence revealed few major adverse events. Studies had medium methodological quality and in general were applicable to current practice. CONCLUSION Rituximab has been shown to be safe and effective in the treatment of non-renal SLE, especially in terms of disease activity, immunologic parameters and steroid-sparing effect. However, it can only be recommended for organ-specific manifestations such as arthritis and thrombocytopaenia. High-quality studies are needed in order to consider the long-term effects of re-treatment on different organ-specific manifestations.

Cardiovascular Events in Systemic Lupus Erythematosus A Nationwide Study in Spain From the RELESSER Registry

Abstract This article estimates the frequency of cardiovascular (CV) events that occurred after diagnosis in a large Spanish cohort of patients with systemic lupus erythematosus (SLE) and investigates the main risk factors for atherosclerosis. RELESSER is a nationwide multicenter, hospital-based registry of SLE patients. This is a cross-sectional study. Demographic and clinical variables, the presence of traditional risk factors, and CV events were collected. A CV event was defined as a myocardial infarction, angina, stroke, and/or peripheral artery disease. Multiple logistic regression analysis was performed to investigate the possible risk factors for atherosclerosis. From 2011 to 2012, 3658 SLE patients were enrolled. Of these, 374 (10.9%) patients suffered at least a CV event. In 269 (7.4%) patients, the CV events occurred after SLE diagnosis (86.2% women, median [interquartile range] age 54.9 years [43.2–66.1], and SLE duration of 212.0 months [120.8–289.0]). Strokes (5.7%) were the most frequent CV event, followed by ischemic heart disease (3.8%) and peripheral artery disease (2.2%). Multivariate analysis identified age (odds ratio [95% confidence interval], 1.03 [1.02–1.04]), hypertension (1.71 [1.20–2.44]), smoking (1.48 [1.06–2.07]), diabetes (2.2 [1.32–3.74]), dyslipidemia (2.18 [1.54–3.09]), neurolupus (2.42 [1.56–3.75]), valvulopathy (2.44 [1.34–4.26]), serositis (1.54 [1.09–2.18]), antiphospholipid antibodies (1.57 [1.13–2.17]), low complement (1.81 [1.12–2.93]), and azathioprine (1.47 [1.04–2.07]) as risk factors for CV events. We have confirmed that SLE patients suffer a high prevalence of premature CV disease. Both traditional and nontraditional risk factors contribute to this higher prevalence. Although it needs to be verified with future studies, our study also shows—for the first time—an association between diabetes and CV events in SLE patients.

Biological therapy for systemic vasculitis: a systematic review.

OBJECTIVE Relapses and failure are frequent in systemic vasculitis (SV) patients. Biological agents have been prescribed as rescue therapies. The aim of this systematic review is to analyze the current evidence on the therapeutic use of biological agents for SV. METHODS MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched up to the end of April 2013. Systematic reviews and meta-analysis, clinical trials, cohort studies, and case series with >3 patients were included. Independent article review and study quality assessment was done by 2 investigators with consensus resolution of discrepancies. RESULTS Of 3447 citations, abstracts, and hand-searched studies screened, 90 were included. Most of the studies included ANCA-associated vasculitis (AAV) patients and only a few included large vessel vasculitis (LVV) patients. Rituximab was the most used agent, having demonstrated efficacy for remission induction in patients with AAV. A number of studies used different anti-TNFα agents with contrasting results. A few uncontrolled studies on the use of abatacept, alemtuzumab, mepolizumab, and tocilizumab were found. CONCLUSION Current evidence on the use of biological therapies for SV is mainly based on uncontrolled, observational data. Rituximab is not inferior to cyclophosphamide for remission induction in AAV and might be superior in relapsing disease. Infliximab and adalimumab are effective as steroid-sparing agents. Etanercept is not effective to maintain remission in patients with granulomatosis with polyangiitis, and serious adverse events have been reported. For LVV, both infliximab and etanercept had a role as steroid-sparing agents, and tocilizumab might be effective also for remission induction in LVV.

Efficacy and safety of nonbiologic immunosuppressants in the treatment of nonrenal systemic lupus erythematosus: a systematic review.

To analyze the efficacy and safety of nonbiologic immunosuppressants in the treatment of nonrenal systemic lupus erythematosus (SLE).

Comprehensive Description of Clinical Characteristics of a Large Systemic Lupus Erythematosus Cohort from the Spanish Rheumatology Society Lupus Registry (RELESSER) With Emphasis on Complete Versus Incomplete Lupus Differences

AbstractSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement and pronounced racial and ethnic heterogeneity. The aims of the present work were (1) to describe the cumulative clinical characteristics of those patients included in the Spanish Rheumatology Society SLE Registry (RELESSER), focusing on the differences between patients who fulfilled the 1997 ACR-SLE criteria versus those with less than 4 criteria (hereafter designated as incomplete SLE (iSLE)) and (2) to compare SLE patient characteristics with those documented in other multicentric SLE registries.RELESSER is a multicenter hospital-based registry, with a collection of data from a large, representative sample of adult patients with SLE (1997 ACR criteria) seen at Spanish rheumatology departments. The registry includes demographic data, comprehensive descriptions of clinical manifestations, as well as information about disease activity and severity, cumulative damage, comorbidities, treatments and mortality, using variables with highly standardized definitions.A total of 4.024 SLE patients (91% with ≥4 ACR criteria) were included. Ninety percent were women with a mean age at diagnosis of 35.4 years and a median duration of disease of 11.0 years. As expected, most SLE manifestations were more frequent in SLE patients than in iSLE ones and every one of the ACR criteria was also associated with SLE condition; this was particularly true of malar rash, oral ulcers and renal disorder. The analysis—adjusted by gender, age at diagnosis, and disease duration—revealed that higher disease activity, damage and SLE severity index are associated with SLE [OR: 1.14; 95% CI: 1.08–1.20 (P < 0.001); 1.29; 95% CI: 1.15–1.44 (P < 0.001); and 2.10; 95% CI: 1.83–2.42 (P < 0.001), respectively]. These results support the hypothesis that iSLE behaves as a relative stable and mild disease. SLE patients from the RELESSER register do not appear to differ substantially from other Caucasian populations and although activity [median SELENA-SLEDA: 2 (IQ: 0–4)], damage [median SLICC/ACR/DI: 1 (IQ: 0–2)], and severity [median KATZ index: 2 (IQ: 1–3)] scores were low, 1 of every 4 deaths was due to SLE activity.RELESSER represents the largest European SLE registry established to date, providing comprehensive, reliable and updated information on SLE in the southern European population.

Registro nacional de pacientes con lupus eritematoso sistémico de la Sociedad Española de Reumatología: objetivos y metodología

OBJECTIVE To describe the objectives, design and methods of the Spanish Society of Rheumatology systemic lupus erythematosus (SLE) registry (RELESSER). METHODS Multicenter, hospital-based registry, with retrospective collection of data from a large representative sample of adult patients with SLE (1997 ACR criteria) attending Spanish rheumatology services. The registry includes demographic data, frequent and infrequent (<1%) clinical manifestations, information about activity, damage, severity, comorbidity, treatments and mortality, collecting 359 variables per patient, with highly standardized definitions. We performed a preliminary descriptive analysis of the data. RESULTS Forty-five centers were involved and 4,024 SLE patients (91% with ≥ 4 ACR criteria) have been included; 90% are women and 93% caucasians, with a median age at diagnosis of 33 years, median disease duration: 120 months, median follow-up duration: 104 months; 3,222 (81%) of the patients are in active follow-up and 591 (14%) were lost to follow-up. The median values of the SELENA-SLEDAI score, SLICC/ACR damage index and Katz severity index have been 2, 1 and 2, respectively. A total of 211 patients (6%) died. CONCLUSIONS RELESSER represents the largest European SLE registry built to date, providing comprehensive and reliable information on SLE manifestations, disease status, comorbid conditions and treatments in daily clinical practice. RELESSER is constituted as a tool of great potential for multicenter clinical research in SLE.

Aplicación de las guías de prevención secundaria de fractura osteoporótica y del índice FRAX en una cohorte de pacientes con fractura por fragilidad

BACKGROUND AND OBJECTIVES There are different guidelines for secondary prevention of fractures related with osteoporosis. Our aim is to analyse the appliance of such guidelines in a sample of patients with fragility fracture PATIENTS AND METHODS Adult patients older than 50 years attended in the emergency department with a fragility fracture were invited to participate in a study for secondary prevention. Clinical data and densitometry for the FRAX index were recorded. Current guidelines were employed to calculate the number of patients who needed secondary prevention. RESULTS With the appliance of current guidelines to 380 patients, 54-100% of women and 26-81% of men were candidates for treatment. For hip fractures the percentage was 81-100% and for forearm fractures 36-93%. FRAX index for hip fracture was ≥3% in 35% of patients. The National Institute for Health and Clinical Excellence and the National Osteoporosis Foundation 2009 were the most restrictive guidelines (54% and 57% respectively). On the other hand the National Guideline Clearinghouse (87%) and the National Osteoporosis Guideline Group (93%). CONCLUSION There are high differences in the percentage of patients who need treatment to prevent new fractures according to the guidelines. Fewer patients require treatment when the FRAX index is included in a guideline.

Efficacy of Raynaud's phenomenon and digital ulcer pharmacological treatment in systemic sclerosis patients: a systematic literature review

Abstract To evaluate the efficacy of current treatments for the Raynaud phenomenon (RP) in patients with systemic sclerosis (SSc), a systematic literature search was performed using Medline, EMBASE, and Cochrane Central Register of Controlled Trials (from 1961 to October 2011). We included meta-analyses, systematic reviews, clinical trials, and high-quality cohort studies published in English or Spanish. Patient populations had to include adults diagnosed with limited cutaneous or diffuse SSc who had associated RP and/or digital ulcers under pharmacological treatment. Efficacy of treatments was evaluated based on: number of RP episodes, RP severity, episode-free time, ulcer improvement/healing, and appearance of new ulcers. We used the Jadad scale of methodological quality to evaluate the quality of randomized clinical trials, and the 2009 Oxford Centre for Evidence-Based Medicine classification for other studies. Of a total of 1617 studies identified, only 27 fulfilled inclusion criteria. Drugs received the following grade recommendations: Grade A for nifedipine, nicardipine, quinapril, IV iloprost, bosentan, tadalafil, and MQx-503; Grade B for beraprost, cicaprost, DMSO, cyclofenil, and atorvastatin; and Grade C for misoprostol, prazosin, OPC-2826, enalapril, sildenafil, antioxidant, and stanazolol. Calcium channel blockers, prostanoids, tadalafil, and bosentan received the highest recommendation level for their effectiveness. However, most systematic reviews reviewed just a handful of studies with small sample sizes and short follow-ups. Our review shows that the existing evidence on the efficacy of RP treatment in SSc patients is inconclusive which calls for further research, especially in the form of prospective studies of high quality with long-term follow-ups.

Consenso de la Sociedad Española de Reumatología sobre el uso de terapias biológicas en el lupus eritematoso sistémico

OBJECTIVE To provide a reference to rheumatologists and other physicians involved in the treatment of systemic lupus erythematosus (SLE) who are using, or about to use biologic therapies. METHODS Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and degree of recommendation were classified according to a model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through a Delphi technique. RESULTS We have produced recommendations on the use of belimumab, the only biological agent with approved indications for SLE, and other biological agents without an indication for SLE. The objective of treatment is to achieve a complete clinical response, taken as the absence of perceived or evident disease activity. Nuances regarding the use of biologic therapies in SLE were reviewed as well, such as the evaluation that should be performed prior to administration and the follow up of patients undergoing these therapies. CONCLUSIONS We present the SER recommendations for the use of biological therapies in patients with SLE.

Healthy lifestyle habits for patients with systemic lupus erythematosus: A systemic review

OBJECTIVES To assess the effects of lifestyle habits on the disease activity and damage, the occurrence of flares and quality of life of people with systemic lupus erythematosus (SLE). METHODS A systematic literature review was performed. MEDLINE, EMBASE, and SCI/SSCI were searched. Experimental and observational studies evaluating the effect of lifestyles for SLE patients were included. Two independent reviewers selected studies and extracted relevant data. Critical appraisal of the studies was assessed following SIGN criteria. RESULTS Eligibility criteria were met by 21 studies, five analyzed the effect of tobacco consumption, nine the effect of physical exercise and seven the effect of diet. Three studies on tobacco observed an association with increased SLE activity and the onset of cutaneous damage. The studies on physical exercise, of heterogeneous quality, reported that aerobic activity is safe for SLE patients, leading to an increase of tolerance to exercise, physical and functional capacity for those with moderate or low activity. A reduction in fatigue, anxiety and depression, as well as improved quality of life, is also suggested though evidence for these outcomes is limited. Better-quality studies on diet analyzed the effect of polyunsaturated fatty acids on disease activity. Three of the four randomized placebo-controlled trials revealed a positive effect both on overall SLE indices and individual symptoms that affect patients. CONCLUSIONS Tobacco smoking increases the risk of skin damage and disease activity in patients with SLE. A diet rich in polyunsaturated fatty acids, avoiding a sedentary lifestyle and supervised exercise should be recommended for patients with stable SLE.