Abstract 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.
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 non–placebo‐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.
Abstract Objectives To evaluate the association between smoking and clinical parameters and structural damage in axial spondyloarthritis (axSpA). Methods We systematically searched MEDLINE, EMBASE ...and Cochrane Library till November 2015. We selected articles that analysed the smoking impact on disease activity, functional status, structural damage, physical mobility and life quality. Independent extraction of articles by 2 authors using predefined data fields was performed. Studies quality was graded according to the Oxford Level of Evidence scale. Results A total of 17 articles were selected for inclusion: 2 case–control, 11 cross-sectional and 4 prospective cohort studies, which analysed 4694 patients. Weak evidence suggested a smoking effect on pain, overall assessment of health, disease activity, physical mobility and life quality in ankylosing spondylitis (AS). Moderate-good evidence revealed higher HAQ-AS among smokers (0.025 units/y; 95% CI: 0.0071–0.0429; p = 0.007). Every additional unit of ASDAS resulted in an increase of 1.9 vs. 0.4 mSASSS units/2 y in AS smokers vs. non-smokers. Good evidence revealed that cigarette smoking and smoking intensity was associated with spinal radiographic progression in axSpA mSASSS ≥2 units/2 y: OR = 2.75, 95% CI: 1.25–6.05, p =0.012; mSASSS progression in heavy smokers (>10 cigarettes/d): OR = 3.57, 95% IC: 1.33–9.60, p = 0.012. Conclusions Published data indicate that smoking has a dose-dependent impact on structural damage progression in axSpA. There is worse HAQ among AS smokers compared to non-smokers. Respect to pain, overall assessment of health, disease activity, physical mobility and life quality, although the evidence level is poor, all evidence points in the same direction: smoking AS patients are worse than non-smoking.
We previously described that fibroblast-like cells from the synovium of rheumatoid arthritis patients (RASFib) constitutively express intracellular and surface IL-15, which induces activation of ...cocultured T cells. Our objective was to study the effect of RASFib IL-15 expression on the function of human CD4(+)CD25(+) regulatory T cells (Treg). RASFib, through their constitutive IL-15 expression, were able to induce the proliferation of human Tregs stimulated through their TCR, and at the same time potentiated their suppressive action on the cytokine secretion of CD4(+)CD25(-) responder T cells (Tresp). In parallel, constitutive RASFib IL-15 expression mediated an up-regulated response of Tresp. Subsequently, total CD4(+) T cells, containing natural proportions of Treg and Tresp, secreted an increased amount of pathogenic cytokines when cocultured with RASFib despite the presence of proliferating Treg with superior regulatory potency. In summary, RASFib IL-15 exerts a dual action on the equilibrium between Treg and Tresp by potentiating the suppressive effect of Treg while augmenting the proinflammatory action of Tresp; the result is a shift of the Treg/Tresp balance toward a proinflammatory state. This alteration of the Treg/Tresp equilibrium is not observed in the presence of osteoarthritis synovial fibroblasts or dermal fibroblasts, which do not constitutively express surface IL-15. Additionally, Treg with superior suppressive potency were present in the peripheral blood and the synovial fluid of RA patients, but this enhanced immunoregulatory activity was not able to overcome the increased secretion of pathogenic cytokines by RA-Tresp, indicating that rheumatoid arthritis patients demonstrate an altered Treg/Tresp equilibrium in vivo.
Objective
To study prognostic factors in different types of idiopathic inflammatory myopathies (IIM) associated with interstitial lung disease (ILD).
Patients and methods
Multicenter retrospective ...study of a Spanish cohort of patients diagnosed with IIM. Patients were classified into four categories: polymyositis (PM), dermatomyositis (DM), antisynthetase syndrome (ASS), and overlap myositis (OM). Sociodemographic data, clinical characteristics, antibodies, and treatments were collected. Cox regression models were calculated to identify factors associated with mortality, the necessity for long-term oxygen therapy (LTOT), and deterioration in respiratory function tests (RFT).
Results
The number of patients included was 478, of whom 112 (23.4%) suffered from ILD: 17% PM, 16% DM, 45% ASS, and 22% OM. Factors associated with mortality in the multivariate analysis were clinically meaningful progression of ILD after 3 months (CMP 3m) (hazard ratio (HR) 9.48,
p
= 0.005), severe infections (HR 6.41,
p
= 0.016), heliotrope erythema (HR 31.1,
p
= 0.002), delay in diagnosis (HR 1.29;
p
= 0.011), and Raynaud’s phenomenon (HR 11.9,
p
= 0.007). However, being female (HR 0.19,
p
= 0.044) and positivity solely for ANAs (HR 0.08,
p
= 0.008) presented a protective effect. CMP 3m (HR 22.7,
p
= 0.027) was associated with the need for LTOT, while basal aldolase (HR 0.90;
p
= 0.049) had a protective effect. Likewise, joint manifestations (HR 0.04,
p
= 0.034) were shown to reduce risk of deterioration in RFT.
Conclusions
CMP 3m, severe infections, delay in diagnosis, heliotrope erythema, and Raynaud’s phenomenon were identified as factors of poor prognosis in different IIM associated with ILD.
The aim of this study is to compare the efficacy and safety of biological therapy with cyclosporin A (CsA), azathioprine (AZA), or placebo in uveitis flares and other ocular outcomes in patients with ...Behçet disease. A comprehensive and sensitive search in MEDLINE, EMBASE, and the Cochrane Library was performed. We selected articles including: (1) adult patients with Behçet’s and uveitis; (2) on biological therapies; (3) placebo or active control with CsA or AZA; (4) analyzing efficacy (number of uveitis flares, macular edema, etc.) and/or safety outcomes. Meta-analyses, systematic reviews, clinical trials, and observational studies with > 10 patients were included. The selection, data collection and quality assessment (Oxford scale) was carried out by 2 reviewers independently. Nine articles of moderate quality were included (6 randomized clinical trials and 3 retrospective studies) involving 378 patients. Most of them, apart from the study drugs received systemic corticosteroids and other immunosuppressant drugs. Infliximab was more effective than CsA in reducing short-term uveitis flares and severe complications of retinal vasculitis in the long term. Rituximab was similar to a combination of cytotoxic drugs in improving inflammatory activity. In patients with active uveitis adalimumab was associated with a lower risk of uveitic flare or visual impairment, and in patients with inactive uveitis to a significantly lowered the risk of flare upon corticosteroid withdrawal. Secukinumab and daclizumab were not superior to placebo in reducing uveitis flares, like interferonα compared to other drugs. Our results highlight the need for better designed comparative studies on Behçet’s uveitis.
Idiopathic inflammatory myopathies (IIMs), also known as autoimmune myositis, are a rare group of autoimmune disorders with a heterogenoeous spectrum of muscular and extramuscular involvement. IIM ...can be classified into several subgroups: dermatomyositis (DM), including clinically amyopathic DM, antisynthetase syndrome (ASS), immune-mediated necrotizing myopathy, inclusion body myositis, polymyositis, and overlap myositis (OM). Skin disease is a defining feature of DM, also present in AAS and OM. Lesions of DM are very varied but many share common histological features that are very useful for an early diagnosis of IIM when cutaneous involvement precedes other symptoms. Although the characteristic signs of DM are heliotrope rash, Gottron’s papules, and Gottron’s sign, there are a multitude of other cutaneous findings that can suggest a diagnosis of DM. Myositis-specific autoantibodies an myositis-associated autoantibodies have been identified in IIM. The former is only present in IIM and the latter can occur not only in IIM but also in other autoimmune disorders such as systemic lupus erythematosus, Sjögren syndrome, or systemic sclerosis. Myositis autoantibodies identify different clinical phenotypes, so they are very valuable in improving diagnosis and classification of IIM patients. This article first discusses the cutaneous findings of DM and then two particular phenotypes, MDA-5 DM, and AAS. Finally, OM according to myositis-associated autoantibodies is reviewed.
Background Plasma concentrations of lipoprotein (a) (Lp(a)), a lipoprotein with atherogenic and thrombogenic properties, have a strong genetic basis, although high concentrations of Lp(a) have also ...been reported in the context of inflammation, as in rheumatoid arthritis (RA). Few studies evaluate the impact of biologic therapies (BT) on Lp(a) in RA, taking into account that with these new therapies a better control of inflammation is achieved. Objective The aim of the study was to evaluate the plasma concentrations of Lp(a) in Spanish RA patients on BT attending rheumatology outpatient clinics. Methods Baseline analysis of the CARdiovascular in rheuMAtology project, a 10-year prospective study, evaluating the risk of cardiovascular events in RA and other forms of inflammatory arthritis. RA patients were classified according to treatment: no biologic, anti-tumor necrosis factor, anti-interleukin-6 receptor tocilizumab (TCZ), and other biologic (rituximab or abatacept). A model of linear multivariate regression was built in which the dependent variable was Lp(a) concentration and the explanatory variable was BT. The model was adjusted for confounding factors. Results Seven hundred and seventy-five RA patients were analyzed. Plasma concentrations of total cholesterol and triglyceride were significantly higher in TCZ-treated patients. Nevertheless, no significant difference in the atherogenic index between TCZ-treated patients and patients without BT was found. After adjusting for confounding factors, patients with BT had lower concentrations of Lp(a) than those without BT; however, only TCZ-treated patients achieved statistically significant differences (β: −0.303, 95% confidence interval: −0.558 to −0.047; P = .02). Conclusions RA patients treated with TCZ show lower plasma concentrations of Lp(a) compared with patients without BT.
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