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.
Non-infectious non-anterior uveitis (NINA) is a sight-threatening condition that often requires immunomodulatory drugs (IMDs) for its management.
To evaluate the published evidence regarding the use ...of IMDs in adult patients with NINA uveitis including intermediate (IU) and posterior uveitis (PU), panuveitis (PanU) and macular edema (ME).
We performed a systematic literature review. Search strategies were designed for Medline, Embase, and Cochrane Libraries for articles up to 2019 to evaluate the efficacy and safety of the IMDs. A quality assessment was performed using the Jadad Scale.
Nineteen randomized clinical trials were selected from the 1,103 articles retrieved. Characteristics of patients, treatment dosages and outcome measures were heterogeneous. The outcomes most frequently analyzed were visual acuity (VA), macular thickness and vitreous haze (VH). Different IMDs were used at their usual dosages. Methotrexate (MTX), micophenolate mofetil, cyclosporine A (CsA), tacrolimus, adalimumab and sarilumab were effective in NINA uveitis. Rituximab combined with MTX was effective in PU. Interferon-β was superior to MTX, albeit with more adverse events in IU with ME. CsA was similar to cyclophosphamide (Cyc) in Behçet uveitis. Tacrolimus was safer and similar to CsA. Cyc was effective in serpiginoid choroiditis, but when combined with azathioprine in PU, but did not improve VA. Secukinumab did not prevent NINA uveitis recurrences, although intravenously it showed a higher response rate than when used subcutaneously. Daclizumab did not show any benefits in Behçet NINA uveitis.
Several IMDs and their combinations can be useful in treating NINA uveitis. The available studies were heterogeneous regarding patient characteristics and outcomes.
Choroidal thickness (CT) has been evaluated as a marker of systemic inflammation in ankylosing spondylitis (AS). This study evaluates the CT of AS patients before and after 6 months of biological ...treatment.
This longitudinal multicenter study evaluated CT in 44 AS patients. The correlations between CT and C-reactive protein (CRP) with disease activity indices were calculated. The concordance between CT and CRP was determined. We assessed factors associated with response to treatment. Clinically important improvement was defined as a decrease in Ankylosing Spondylitis Disease Activity Score of 1.1 points or greater.
Forty-four eyes in patients aged 18 to 65 years were included. Mean CT values were significantly higher at baseline than after 6 months of treatment (baseline: 355.28 ± 80.46 μm; 6 months: 341.26 ± 81.06 μm; p < 0.001). There was a 95% concordance between CT and CRP at baseline and 6 months. Clinically important improvement was associated with lower baseline CT and age as independent factors (odds ratios, 0.97 95% confidence interval, 0.91-0.93; p = 0.009 and 0.81 95% confidence interval, 0.7-0.95; p = 0.005), with baseline CT of less than 374 μm (sensitivity 78%, specificity 78%, area under the curve 0.70, likelihood ratio 3.6).
Choroidal thickness decreased significantly after 6 months of biological treatment in all treatment groups. Choroidal thickness and CRP had a 95% concordance. A high CT was associated with a risk of biological treatment failure. Choroidal thickness can be considered a useful biomarker of inflammation and a factor associated with response to treatment in AS.
The intestinal immune response could play an important role in obesity-related comorbidities. We aim to study the profile of duodenal cytokines and chemokines in patients with morbid obesity (MO), ...its relation with insulin resistance (IR) and the intake of metformin, and with the evolution of MO after sleeve gastrectomy (SG).
Duodenal levels of 24 cytokines and 9 chemokines were analyzed in 14 nonobese and in 54 MO who underwent SG: with lower IR (MO-lower-IR), with higher IR (MO-higher-IR), and with type 2 diabetes treated with metformin (MO-metf-T2DM).
MO-lower-IR had higher levels of cytokines related to Th1, Th2, Th9, Th17, Th22, M1 macrophages, and chemokines involved in the recruitment of macrophages and T-lymphocytes (p < 0.05), and total (CD68 expression) and M1 macrophages (ITGAX expression) (p < 0.05) when compared with nonobese patients, but with a decrease in M2 macrophages (MRC1 expression) (p < 0.05). In MO-higher-IR, these chemokines and cytokines decreased and were similar to those found in nonobese patients. In MO-metf-T2DM, only IL-4 (Th2) and IL-22 (Th22) increased their levels with regard to MO-higher-IR (p < 0.05). In MO-higher-IR and MO-metf-T2DM, there was a decrease of CD68 expression (p < 0.05) while ITGAX and MRC1 were similar with regard to MO-lower-IR. We found an association between CXCL8, TNFβ and IL-2 with the evolution of body mass index (BMI) after SG (p < 0.05).
There is an association between a higher IR and a lower duodenal immune response in MO, with a slight increase in those patients with metformin treatment. Intestinal immune response could be involved in the evolution of BMI after SG.
To evaluate the response to hepatitis B virus (HBV) vaccine in patients on biological therapy. Adults with autoimmune inflammatory diseases on biological therapy such as anti-TNFα, rituximab, ...tocilizumab, abatacept, or anakinra were included. Hepatitis B surface antibody (anti-HBs) was measured by ELISA before and after vaccination. Seroconversion was considered when an anti-HBs titer > 10 mIU/mL was achieved. The effect of treatment on the immunoprotective state was studied. The response was compared with that obtained in patients on synthetic disease modifying anti-rheumatic drugs (DMARDs) and healthy controls. A total of 187 patients on biologicals, 48 on synthetic DMARDs, and 49 on healthy controls were analyzed. More than 80% of patients on biologics responded to the vaccine but required more boosters and second vaccine series. Patients who achieved seroconversion were younger than those who did not (47.10 ± 12.99 vs. 53.18 ± 10.54 years,
p
= 0.012). Being on etanercept or golimumab was associated with seroconversion, while being on rituximab was not. Seroconversion was achieved in 93.75% of patients on synthetic DMARDs and 97.96% of healthy controls. The seroconversion rate in the biologics group was lower than in the synthetic DMARD group (
p
= 0.043) and tended to be lower than in the healthy group (
p
= 0.056). In patients on biological therapy, a high rate of HBV vaccine response can be achieved when a complete vaccination schedule is administered. Vaccination while not on biological agents reduces the requirement for boosters and revaccination.
Key points:
• Patients on biological therapy can achieve high rates of immune response to HBV vaccine when complete vaccination schedules are administered.
• However, to achieve such a high seroconversion rate, more boosters and second vaccination series are required.
• This supports the proposal already made to provide HBV vaccination to all patients with an autoimmune inflammatory disease after the diagnosis is made and not when the use of a biological treatment is under consideration.
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.
Background:
Spondyloarthritis (SpA) is a group of related but phenotypically distinct inflammatory disorders that include axial SpA (axSpA) and psoriatic arthritis (PsA). Information on the ...characteristics and management of these patients in the real world remains scarce.
Objectives:
To explore the characteristics and management disease activity assessment and treatment with secukinumab (SEC) or other biologic disease-modifying antirheumatic drugs (bDMARDs) of axSpA and PsA patients using natural language processing (NLP) in Electronic Health Records (EHRs).
Design:
National, multicenter, observational, and retrospective study.
Methods:
We analyzed free-text and structured clinical information from EHR at three hospitals. All adult patients with axSpA, PsA or non-classified SpA from 2018 to 2021 with minimum follow-up of three months were included when starting SEC or other bDMARDs. Clinical variables were extracted using EHRead® technology based on Systemized Nomenclature of Medicine-Clinical Terms (SNOMED CT) terminology.
Results:
Out of 887,735 patients, 758 were included, of which 328 had axSpA 58.5% male; mean (SD) age of 50.7 (12.7) years, 365 PsA 54.8% female, 53.9 (12.4) years, and 65 non-classified SpA. Mean (SD) time since diagnosis was 36.8 (61.0) and 24.1 (35.2) months for axSpA and PsA, respectively. Only 116 axSpA patients (35.3%) had available Ankylosing Spondylitis Disease Activity Score (ASDAS) or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at bDMARD onset, of which 61 presented active disease. Disease Activity in PSoriatic Arthritis (DAPSA) or Disease Assessment Score - 28 joints (DAS-28) values at bDMARD onset were available for only 61 PsA (16.7%) patients, with 23 of them having active disease. The number of patients with available tender joint count or swollen joint count assessment was 68 (20.7%) and 59 (18%) for axSpA, and 115 (31.5%) and 119 (32.6%) for PsA, respectively. SEC was used in 63 (19.2%) axSpA patients and in 63 (17.3%) PsA patients.
Conclusion:
Using NLP, the study showed that around one-third of axSpA and one-sixth of PsA patients have disease activity assessments with ASDAS/BASDAI or DAPSA/DAS-28, respectively, highlighting an area of improvement in these patients’ management.
Plain language summary
Investigating axial spondyloarthritis and psoriatic arthritis patients using natural language processing
We conducted a study in Spain to better understand patients with specific rheumatic conditions known as axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). To analyze their characteristics, we used a computer technology called EHRead, which uses Natural Language Processing (NLP) to analyze free text from electronic health records. Out of a large group of patients, we focused on 758 individuals who had axSpA or PsA. Most of the axSpA patients were men, and they were around 51 years old on average. For the PsA patients, most were women, and their average age was about 54 years. We analyzed outcomes and treatments of these patients. Our findings showed that we can describe and assess a cohort of patients from real world using NLP. Besides, only about one-third of axSpA patients and one-sixth of PsA patients had their respective outcomes completely assessed, which indicates that there is potential room for improvement in the management of axSpA and PsA. The most promising feature in our study is the use of NLP, an artificial intelligence technology that helps us understand information in medical records written in free text. This can help us explore the characteristics of patients and their management in the real world, bringing an opportunity to enhance the care of patients with axSpA and PsA.
Influenza vaccine is recommended for patients with autoimmune inflammatory diseases (AIID) on biological therapy.
To evaluate whether serological response to Influenza vaccine obtained in patients on ...biological therapy is similar to that achieved in patients on synthetic disease-modifying anti-rheumatic drugs (DMARDs) and that obtained in healthy controls.
We designed a cohort study in which patients with AIID, 68 on biological therapy and 46 on synthetic DMARDs, as well as 48 healthy controls, were included and vaccinated during the 2015-2016 influenza season. ELISA was used to measure Influenza antigen (Ag) A and B antibodies, before and after vaccination.
After vaccination, 88.24% of patients on biologics, 71.74% of those on synthetic DMARDs and 89.58% of healthy controls, presented detectable antibodies against antigen A, while 42.65% of subjects on biologics, 41.30% of those on DMARDs and 54.17% of healthy subjects were seropositive against Ag B. We did not find statistical differences.
In our study, biological therapy is not associated with worse serological response.
ObjectiveTo evaluate whether immunological response to influenza vaccination is impaired in patients who are receiving secukinumab.Patients and methodsSubjects suffering from psoriatic arthritis or ...ankylosing spondylitis who were receiving treatment with secukinumab and healthy volunteers were included.All participants received seasonal inactivated trivalent influenza vaccine recommended by the WHO in the 2017–2018 northern hemisphere influenza season, which contained an A/Michigan/45/2015 (H1N1)pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus and a B/Brisbane/60/2008-like virus.Haemagglutination inhibition was used to evaluate basal antibody (Ab) titres against the three influenza vaccine virus strains just before vaccination and at least 4 weeks after the vaccine administration. Response to vaccine was considered as >4-fold increases in Ab titre.ResultsThirty subjects, 17 patients and 13 healthy controls, with a follow-up duration of 33±8 days, were analysed. There were no demographic differences between groups. Patients and controls achieved a median of 4.6-fold and 4.0-fold increases, respectively, for anti H1N1 and almost 4.0 (3.7) for patients and 5.3 for controls for anti-B Ab. Both groups presented a poor response against H3N2, with <1.5-fold increase. Seroconversion rates were similar in both groups. Secukinumab did not influence the response to the influenza vaccine (relative risk: 1.09 (95% CI 0.58 to 2.07) for H1N1, RR: 1.53 (95% CI 0.15 to 15.0) for H3N2 and RR: 0.72 (95% CI 0.32 to 1.83) for B strain).ConclusionIn our study, secukinumab has no effect on the immunogenic response to the influenza vaccine.
The aim of this study was to describe the characteristics of patients with uveitis associated with an immunologic or idiopathic disease that requires immunosuppressive treatment and the response to ...such treatments in real clinical practice.
An observational, descriptive, longitudinal, and retrospective study of a cohort of patients diagnosed with noninfectious uveitis was performed. To assess the response to treatment, we evaluated the change in visual acuity, vitritis, and the presence of macular edema.
We included 356 patients. Overall, 12% required treatment with systemic corticosteroids, and 66 patients (18.5%) required immunosuppressive/biological treatment, with methotrexate being the most used (55%). Immunosuppressive drugs were used in 59 cases (in 56 patients, as the first choice of treatment and for 3 patients as the second choice after treatment with biologics). Treatment with biologics was the first choice in 10 patients out of 66 (15%), and 34 (48%) required them at some time during the disease, with adalimumab being the most commonly used. Thirty-five patients (53%) needed to switch drugs due to a lack of response to the first one. There were no differences between different drugs in the resolution of vitritis and improvement in vision.
The use of systemic corticosteroids and immunosuppressive/biologics was necessary for a high number of patients with noninfectious uveitis. In our series, tocilizumab was significantly more effective in the resolution of macular edema.
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