Description and Prevalence of Spondyloarthritis in Patients with Anterior Uveitis: The SENTINEL Interdisciplinary Collaborative Project.

PURPOSE: To describe and analyze the prevalence of spondyloarthritis (SpA) in patients with anterior uveitis (AU). DESIGN: Multicentric, observational, prospective study. PARTICIPANTS: Consecutive patients with AU who were human leukocyte antigen (HLA)-B27 positive or HLA-B27 negative with more than 1 episode of AU separated by at least 3 months were selected. Patients with a previous diagnosis of SpA were excluded. METHODS: Included patients were evaluated by an ophthalmologist and a rheumatologist following a predefined visit schedule. MAIN OUTCOME MEASURES: Sociodemographic and clinical variables including the diagnosis of SpA according to Assessment of SpondyloArthritis International Society (ASAS) criteria and an exhaustive ophthalmological examination (best-corrected visual acuity, intraocular pressure, biomicroscopic examination of the anterior and posterior segment of the eye, cataract evaluation, optical coherence tomography evaluating both the 1-mm central retina thickness and the optic nerve head and retinal nerve fiber layer, and visual field in a dark room with 1 eye patched) were collected. Baseline descriptive, bivariate, and concordance analyses were performed. RESULTS: We included 798 patients, mostly men (59%) with a mean age of 45 years; 60% were AU HLA-B27 positive, and 40% had recurrent negative AU HLA-B27. A total of 50.2% and 17.5% of patients presented axial and peripheral SpA according to ASAS criteria, respectively. Patients with AU who were HLA-B27 positive were more frequently diagnosed with axial (69.8% vs. 27.3%, P < 0.0001) and peripheral SpA (21.9% vs. 11.1%, P < 0.0001) than patients with recurrent negative AU HLA-B27. In general, we did not detect important differences between groups in the ophthalmologic variables. CONCLUSIONS: A large percentage of patients with clinically significant AU have an undiagnosed SpA. This percentage is even higher if the HLA-B27 haplotype is positive.

Identification of lymphoma predictors in patients with primary Sjögren's syndrome: a systematic literature review and meta-analysis.

To identify risk and predictors of lymphoma or lymphoproliferative disease in patients with primary Sjögren syndrome. Articles were identified through a comprehensive search strategy in Medline, Embase and Cochrane CENTRAL. Studies had to investigate primary Sjögren syndrome patients, 18 years of age or older, with the goal of examining potential clinical, immunological and hematological risk factors for lymphoma or lymphoproliferative disease. The quality of the studies was graded using the Oxford Levels of Evidence Scale. Whenever possible, the authors created evidence tables and performed meta-analysis. Of 900 studies identified, 18 were selected for inclusion. These studies provided data from over 15,000 patients (90 % female) for analysis. Lymphadenopathy, parotid enlargement, palpable purpura, low C4 serum levels and cryoglobulins were the most consistent non-Hodgkin´s lymphoma/lymphoproliferative disease predictors. Additionally, some of the studies identified splenomegaly, low C3 serum levels, lymphopenia and neutropenia as significant prognostic factors. The detection of germinal center-like lesions in primary Sjögren Syndrome diagnostic salivary biopsies was also proposed as highly predictive of non-Hodgkin´s lymphoma. In contrast, anemia, anti-Ro, anti-La, antinuclear antibodies, rheumatoid factor, male gender and hypergammaglobulinemia were not associated with lymphoma or lymphoproliferative disease. Patients with primary Sjögren syndrome have an increased risk of lymphoma or lymphoproliferative disease compared to the general population. Ascertaining relevant and reliable predictors in this patient population would greatly facilitate the identification of patients at elevated risk for closer monitoring in the context of limited resources.

Serious infections in patients with rheumatoid arthritis and other immune-mediated connective tissue diseases exposed to anti-TNF or rituximab: data from the Spanish registry BIOBADASER 2.0.

Data on infections in patients exposed to biologic therapies are mainly focused on rheumatoid arthritis (RA). Little is known about the safety profile in other immune-mediated connective tissue diseases (ICTD). The purpose of this study was to describe and to compare the risk of serious infections (SI) in patients with RA and other ICTD on anti-TNF or rituximab and to identify predictors of SI. We analyzed RA or other ICTD patients on anti-TNF or rituximab included in the Spanish registry BIOBADASER 2.0 (2000-2011). For each disease group, incidence rate (IR), mortality rate (MR) and IR ratio (IRR) of SI with 95% CI were estimated. Risks were then standardized by age and sex to the general population. Risk factors for SI were assessed by Poisson regression models. A total of 3,301 patients on anti-TNF (n = 3,166) or rituximab (n = 135), of which 176 (5%) had ICTD other than RA, were analyzed. IR of SI was higher in non-RA ICTD than in RA, with an IRR of 3.15 (95% CI 1.86, 5.31) before adjustment and 1.96 (95% CI 1.06, 3.65) after adjustment for age, comorbidity and corticoid use. Mortality due to infections was higher in ICTD although it did not reach statistical significance. Age, disease duration, comorbidities, corticosteroids and ICTD different to RA were all independently associated with SI. Patients with ICTD other than RA are at a high risk of SI when prescribed anti-TNF or rituximab, partly due to the excess comorbidity and immunosuppressive co-treatment, but also to the inflammatory disease. When evaluating the risk/benefit ratio of off-label medications in ICTD patients, age, comorbidities and corticoid use should carefully be taken into account, applying adequate preventive measures.

Efficacy and safety of the optimisation of biological therapy in non-infectious uveitis: Systematic review.

OBJECTIVE: To conduct a systematic critical review of the literature on the efficacy and safety of biological therapy (BT) optimisation in non-infectious uveitis (NIU). METHODS: Searches were conducted (PubMed, Embase, Cochrane and conference abstracts) up to March 2021. The study population comprised patients with NIU in remission after BT. We analysed BT optimisation strategies. The main outcome measures were efficacy and safety. To assess the risk of bias, the ROBINS-1 tool was used. A qualitative review of the data was performed to assess heterogeneity and bias. Evidence tables (study characteristics and outcomes) were generated, and quantitative synthesis was performed if data were homogeneous. RESULTS: We selected 11 studies (prospective and retrospective) including 513 patients. The studies were at moderate/high risk of bias and there was considerable variability between studies in sample size, underlying diseases, definitions and outcome variables. Criteria for starting optimisation were not uniform. All BTs optimised were TNF inhibitors. Optimisation could be attempted after 3-6 months in remission. Relapse occurred in 25-50% of patients but was controlled after dose re-escalation or BT switching. No safety issues were identified. CONCLUSIONS: The optimization of BT (with TNF inhibitors) has been applied in patients with NIU in remission. There is no consensus on criteria for attempting BT optimisation and protocols are heterogeneous. There is a least moderate risk of bias, so no robust conclusions on efficacy and safety of optimization can be reached. Preliminary evidence suggests that relapses might be controlled using standard doses. Larger studies using uniform criteria are needed.

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.

Systemic 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.

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 Jadad's 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.

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

OBJECTIVE: To analyze the efficacy and safety of nonbiologic immunosuppressants in the treatment of nonrenal systemic lupus erythematosus (SLE). METHODS: We conducted a sensitive literature search in Medline, Embase, and the Cochrane Central Register of Controlled Trials up to October 2011. The selection criteria were studies including adult patients with SLE, a treatment intervention with nonbiologic immunosuppressants, a placebo or active comparator group, and outcome measures assessing efficacy and/or safety. Meta-analyses, systematic reviews, clinical trials, and cohort studies were included. The quality of each study was evaluated using Jadad's scale and the Oxford Levels of Evidence. RESULTS: In total, 158 of the 2,827 initially found articles were selected for detailed review; 65 studies fulfilled the predetermined criteria. Overall, the studies were low quality, with only 11 randomized controlled trials (RCTs). Cyclophosphamide demonstrated efficacy for neuropsychiatric SLE, preventing relapses with an additional steroid sparing effect, although its use was associated with cumulative damage, development of cervical intraepithelial neoplasia,and ovarian failure. Other immunosuppressants (azathioprine, methotrexate, leflunomide, mycophenolate mofetil,and cyclosporin A) demonstrated efficacy in reducing nonrenal activity and flares with a steroid-sparing effect, although only on occasion in non­placebo-controlled RCTs of small numbers of patients. CONCLUSION: Several immunosuppressants demonstrated their safety and efficacy in nonrenal SLE. A specific drug for each particular manifestation cannot be recommended, although cyclophosphamide may be used in more severe cases, and methotrexate may be the first option in most cases of moderately active SLE. High-quality RCTs of larger numbers of patients are needed.

Systematic literature review of bisphosphonates and osteonecrosis of the jaw in patients with osteoporosis.

OBJECTIVE: To systematically assess the literature related to the occurrence of osteonecrosis of the jaw (ONJ) using bisphosphonates (BP) in the treatment of osteoporosis (OP). METHODS: We conducted a systematic literature search in PubMed, EMBASE and the Cochrane Central Register of Controlled Trials up to July 2010, including terms relating to OP, ONJ, and BP (MeSH and free text). We selected meta-analysis, systematic reviews and clinical trials (CT), English or Spanish, including patients > 18 years of both sexes with OP treated with BF (intravenous and oral). Furthermore, studies should evaluate the occurrence of ONJ during treatment with BF. We excluded studies that included patients with cancer or diseases other than OP, animal studies and basic science. The selection of articles both by title and 2 independent reviewers conducted a detailed review of the abstracts. We used the modified Oxford Scale (version 2001) to assess the quality of the included studies. RESULTS: We identified 1422 articles of which we included 18 (8 systematic reviews, 8 CT and 2 meta-analysis). Most studies were of good quality and examined the use of BF in middle-aged women with OP. Frequency of ONJ was low. CONCLUSIONS: We found insufficient evidence to affirm that intravenous or oral BF used exclusively for the treatment of OP lead to a significant risk of ONJ (evidence level 2a, grade B recommendation).

[Are calcium and vitamin D supplements for everyone?: Cons]. / Suplementos de calcio y vitamina D ¿para todos?: Contras.

Calcium and vitamin D supplements are one of the most widely used treatments in the field of bone metabolism and, especially due to its frequency, in the case of the osteoporosis. Sometimes the use of these treatments can be easily justified because there is plenty of evidence or because prescription is mandatory. But other times, not only because of the possibility of adverse events, the indication of these therapies is more controversial. Furthermore, and particularly in the context of osteoporosis, it may be suggested that prescribing calcium and vitamin D supplements to the general population may reduce the impact of disease.

[Consensus statement of the Spanish Society of Rheumatology on the management of biologic therapies in psoriatic arthritis]. / Documento SER de consenso sobre el uso de terapias biológicas en la artritis psoriásica.

OBJECTIVE: Due to the amount and quality variability regarding the use of biologic therapy (BT) in psoriatic arthritis (PsA) patients, the Spanish Society of Rheumatology (SER) has promoted the generation of recommendations based on the best evidence available. These recommendations should serve as reference to rheumatologists and those involved in the treatment of patients with PsA, who are using, or about to use BT. METHODS: Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and degree of recommendation was classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. RESULTS: We have produced recommendations for the use of TB currently available for PsA in our country. These recommendations include disease assessment, treatment objectives, therapeutic scheme and switching. CONCLUSIONS: We present an update on the SER recommendations for the use of BT in patients with PsA.

[Consensus Statement of the Spanish Society of Rheumatology on the management of biologic therapies in spondyloarthritis except for psoriatic arthritis]. / Documento SER de consenso sobre el uso de terapias biológicas en la espondilitis anquilosante y otras espondiloartritis, excepto la artritis psoriásica.

OBJECTIVE: Due to the amount and variability in quality regarding the use of biologic therapy (BT) in patients with spondyloarthritis (SpA), except for psoriatic arthritis (PsA) patients, the Spanish Society of Rheumatology has promoted the generation of recommendations based on the best evidence available. These recommendations should be a reference for rheumatologists and those involved in the treatment of patients with spondyloarthritis (SpA), except for psoriatic arthritis (PsA), who are using, or about to use BT. METHODS: Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and grade of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. RESULTS: We have produced recommendations on the use of BT currently available for SpA (but not PsA) in our country. These recommendations include disease assessment, treatment objectives, therapeutic scheme and switching. CONCLUSIONS: We present an update on the SER recommendations for the use of BT in patients with SpA, except for PsA.

[Management of spondyloarthritis (ESPOGUIA): methodology and general data from the document]. / Guía práctica para el manejo de las espondiloartritis (ESPOGUIA): metodología y datos generales del documento.

BACKGROUND: The need for clinical practice guidelines for spondyloarthritis (SpA) comes from the complexity of its management and the great advances that both its treatment and its diagnosis have experiences, which come accompanied by a great variability in its management that exceeds what is considered acceptable. The objective of the ESPOGUIA is to reduce the variability in the management of SA, improving the quality of care through clinical recommendations adapted to their particular environment and based on the best available evidence. METHODS: For the development of ESPOGUÍA the following methods have been employed: nominal group, systematic review and Delphi surveys. The expert panel is voluntary, with multiple disciplines participating and based on selection criteria. For the first time in a SER recommendation document, the opinion of the patient was included. In a meeting of the nominal group, the reach, objective, users, organization and needs of the systematic review were established. The elaboration of the guideline, along with its recommendations, was performed in parallel to the systematic reviews, with a meeting for agreement held afterward. The scoring of the degree of evidence and the level of the recommendation was established from the evidence levels proposed by the Oxford Center of Evidence-Based Medicine and the degree of agreement was obtained through a two-round Delphi exercise. RESULTS: We have produced a clinical guideline that encompasses all of the SpA, although it has two sub-guidelines, one for ankylosing spondylitis and the other one for psoriatic arthritis. The target users are mainly rheumatologists, although other specialists and paramedical staff, such as nurses or patient associations, might benefit. Its content envelops all of the management aspects of SpA, from clinical suspicion to treatment, follow-up and day-to-day activities of the patient. CONCLUSIONS: ESPOGUIA can become a very useful instrument for the management of SA and an interactive reference.

[Update of the Consensus Statement of the Spanish Society of Rheumatology on the management of biologic therapies in rheumatoid arthritis]. / Actualización del Documento de Consenso de la Sociedad Española de Reumatología sobre el uso de terapias biológicas en la artritis reumatoide.

OBJECTIVE: To provide a reference to rheumatologists and to those involved in the treatment of RA who are using, or about to use biologic therapy. METHODS: Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and grade of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. RESULTS: We have produced recommendations on the use of the seven biologic agents available for RA in our country. The objective of treatment is to achieve the remission of the disease as quickly as possible. Indications and nuances regarding the use of biologic therapy were reviewed as well as the evaluation that should be performed prior to administration and the follow up of patients undergoing this therapy. CONCLUSIONS: We present an update on the SER recommendations for the use of biologic therapy in patients with RA.