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Autoimmunity Reviews Jan 2023Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical peripheral polyarthritis in the hands and/or feet, leading to long-term disability if not... (Review)
Review
BACKGROUND
Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical peripheral polyarthritis in the hands and/or feet, leading to long-term disability if not treated effectively. RA is preceded by a preclinical phase, in which genetically predisposed individuals accumulate environmental risk factors, and during which autoimmunity develops, followed by the emergence of non-specific signs and symptoms before arthritis becomes manifest. Early treatment in at-risk individuals - i.e. before the disease is fully established - has the theoretical potential to delay or prevent disease onset, with a positive impact on both patients' life and society.
OBJECTIVES
We aimed to understand the feasibility of preventive treatment in at-risk individuals, taking into account recently performed studies and ongoing clinical trials, as well as patient perspectives.
METHODS
We performed a systematic literature review (SLR) on Medline and Embase, searching articles published between 2010 and 2021 with the following key-words: "Rheumatoid arthritis", "arthralgia", "pre-treatment" or "prevent".
RESULTS
Our SLR identified a total of 1821 articles. Articles were independently screened by two researchers. A total of 14 articles were included after screening, and an additional 8 reports were manually included. We identified ten relevant clinical trials performed in at-risk individuals, or in individuals with undifferentiated inflammatory arthritis. Although no treatment was shown to prevent RA onset, early treatment with rituximab and abatacept delayed onset of full-blown RA, and both conventional and biological disease-modifying anti-rheumatic drugs (DMARDs) decreased disease-related physical limitations and increased DAS28-defined remission, at least temporarily.
CONCLUSIONS
This SLR demonstrates that early treatment of at-risk individuals may be effective in delaying RA onset, thereby decreasing disease-related limitations in individuals in the pre-clinical phase of RA. Whether this may ultimately lead to prevention of RA remains to be determined.
Topics: Humans; Arthritis, Rheumatoid; Antirheumatic Agents; Abatacept; Rituximab; Autoimmunity
PubMed: 36280095
DOI: 10.1016/j.autrev.2022.103217 -
Frontiers in Pharmacology 2022Rheumatoid arthritis (RA) is a systemic inflammatory disease that affects the synovial fluid of joints, tendons, and some extra-articular sites. Biologic agents have...
Rheumatoid arthritis (RA) is a systemic inflammatory disease that affects the synovial fluid of joints, tendons, and some extra-articular sites. Biologic agents have been highly effective and are comparable in reducing RA symptoms, slowing disease progression, and improving physical function; however, concerns have been raised about the risks of several potential adverse effects. Thus, this study aimed to assess the safety of biological therapy in patients with rheumatoid arthritis in observational studies using administrative health databases. PubMed, Embase, Lilacs, Ovid, Scopus, and Web of Science were searched from inception to 21 October 2021. The analysis was divided into five groups: tumor necrosis factor inhibitors (TNFi) versus non-TNFi; TNFi versus csDMARDs; bDMARDs versus csDMARDs; abatacept versus bDMARDs; and TNFi versus Janus kinase inhibitors (JAKi). The adverse events were cancer, cardiovascular events, infection, herpes zoster, tuberculosis, and death. The methodological quality of the studies was assessed by the Newcastle-Ottawa Scale. A random-effects model estimated risk ratios with 95% confidence intervals. Thirty-one studies were eligible for inclusion in the present systematic review, published from 2014 to 2021. A total of 1,039,398 RA patients were assessed. The 31 studies evaluated eleven different biological drugs. No significant differences were found regarding safety between TNFi versus non-TNFi (RR 1.08; 95% CI 0.92-1.28; < 0.01; I = 93.0%), TNFi versus csDMARDs (RR 0.91; 95% CI 0.75-1.10; < 0.01; I = 87.0%), bDMARDs versus csDMARDs (RR 0.99; 95% CI 0.82-1.20; < 0.01; I = 93.0%), abatacept versus bDMARDs (RR 0.80; 95% CI 0.54-1.18; < 0.01; I = 90.0%), and TNFi versus JAKi (RR 3.54; 95% CI 0.30-42.09; = 0.01; I = 81.0%). In the subgroup analysis, among studies comparing abatacept to TNFi, a lower risk of cardiovascular events was associated with abatacept (RR 0.37; 95% CI 0.24-0.55). Our results do not suggest an increased risk of adverse events associated with biological therapy in treating RA patients, indicating a lower risk of cardiovascular events with abatacept than TNFi. However, these findings must be interpreted with caution given the limitations of this study and the low/very low certainty of the evidence. https://www.crd.york.ac.uk/prospero/display_record.php?, identifier [CRD42020190838].
PubMed: 36034855
DOI: 10.3389/fphar.2022.928471 -
Archives of Rheumatology Jun 2022Biological medications have been used with an increasing frequency to treat rheumatological diseases. Autoimmune events can be induced by these drugs, such as... (Review)
Review
OBJECTIVES
Biological medications have been used with an increasing frequency to treat rheumatological diseases. Autoimmune events can be induced by these drugs, such as psoriasiform lesions, alopecia, lupus and, vasculitis, which more often affects the skin (small-sized vessels) and eventually other organs. In this review, we describe the clinical profile of patients with vasculitis induced by the main biological agents used in rheumatology.
PATIENTS AND METHODS
We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. The PubMed database was used for searching eligible articles. We included case reports, case series, and letter to the editor of patients on anti-tumor necrosis factor-alpha (anti-TNF-a) molecules, as well as tocilizumab, ustekinumab, secukinumab, rituximab, and abatacept, who had vasculitis induced by these agents.
RESULTS
Eighty-one articles were included for final analysis (n=89). Twenty-seven patients were using infliximab, 20 adalimumab, 18 etanercept, seven secukinumab, four certolizumab, four rituximab, three golimumab, three ustekinumab, two abatacept, and one tocilizumab. Unspecific leukocytoclastic vasculitis (LCV) was the most common type of vasculitis (n=37), followed by anti-neutrophil cytoplasmic antibody (ANCA)- associated vasculitis (n=16). The medication was replaced with another biological molecule in 23 cases, with only four relapses. In six cases, the biological was maintained, but vasculitis worsened/persisted in one case, being necessary drug removal.
CONCLUSION
Infections, infusion reaction, cancer, and autoimmune events are well-known side effects of biological therapy. This review demonstrates that vasculitis is another adverse effect of this type of therapy, particularly the anti-TNF-a molecules, and LCV the most reported type of vasculitis.
PubMed: 36017201
DOI: 10.46497/ArchRheumatol.2022.9049 -
The Journal of Rheumatology Jan 2023To determine the risk of not being able to sustain remission after tapering methotrexate (MTX) from targeted therapy in patients with controlled rheumatoid arthritis... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the risk of not being able to sustain remission after tapering methotrexate (MTX) from targeted therapy in patients with controlled rheumatoid arthritis (RA).
METHODS
A systematic literature search was conducted in MEDLINE, Embase, and the Cochrane Library for studies reporting remission outcomes after tapering MTX from targeted therapies in RA. Full-text articles and abstracts reported in English were included. Metaanalyses were conducted using random-effects models. Forest and funnel plots were created.
RESULTS
A total of 10 articles were included. Studies evaluated MTX being tapered from combination treatment with tumor necrosis factor inhibitors, tocilizumab, abatacept, and tofacitinib. A total of 9 studies used a randomized design and 1 was observational. Out of 10 studies, 3 focused on early RA (ie, < 1 yr). The MTX-tapering strategy was gradual in 2 studies and rapid in 8 studies. Follow-up ranged from 3 to 18 months in randomized trials and up to 3 years in the observational study. Our metaanalysis, which included 2000 participants with RA from 10 studies, showed that patients who tapered MTX from targeted therapy had a 10% reduction in the ability to sustain remission and an overall pooled risk ratio of 0.90 (95% CI 0.84-0.97). There was no heterogeneity ( = 0%, = 0.94). Our funnel plot indicated minimal publication bias.
CONCLUSION
Patients with controlled RA may taper MTX from targeted therapy with a 10% reduction in the ability to sustain remission for up to 18 months. Longer follow-up studies with attention to radiographic, functional, and patient-reported outcomes are needed. The risk of disease worsening should be discussed with the patient with careful follow-up and prompt retreatment of disease worsening.
Topics: Humans; Methotrexate; Antirheumatic Agents; Arthritis, Rheumatoid; Abatacept; Tumor Necrosis Factor Inhibitors; Drug Therapy, Combination; Treatment Outcome; Observational Studies as Topic
PubMed: 35970524
DOI: 10.3899/jrheum.220152 -
Transplant Infectious Disease : An... Dec 2022We aimed to analyze the humoral and cellular response to standard and booster (additional doses) COVID-19 vaccination in solid organ transplantation (SOT) and the risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We aimed to analyze the humoral and cellular response to standard and booster (additional doses) COVID-19 vaccination in solid organ transplantation (SOT) and the risk factors involved for an impaired response.
METHODS
We did a systematic review and meta-analysis of studies published up until January 11, 2022, that reported immunogenicity of COVID-19 vaccine among SOT. The study is registered with PROSPERO, number CRD42022300547.
RESULTS
Of the 1527 studies, 112 studies, which involved 15391 SOT and 2844 healthy controls, were included. SOT showed a low humoral response (effect size [ES]: 0.44 [0.40-0.48]) in overall and in control studies (log-Odds-ratio [OR]: -4.46 [-8.10 to -2.35]). The humoral response was highest in liver (ES: 0.67 [0.61-0.74]) followed by heart (ES: 0.45 [0.32-0.59]), kidney (ES: 0.40 [0.36-0.45]), kidney-pancreas (ES: 0.33 [0.13-0.53]), and lung (0.27 [0.17-0.37]). The meta-analysis for standard and booster dose (ES: 0.43 [0.39-0.47] vs. 0.51 [0.43-0.54]) showed a marginal increase of 18% efficacy. SOT with prior infection had higher response (ES: 0.94 [0.92-0.96] vs. ES: 0.40 [0.39-0.41]; p-value < .01). The seroresponse with mRNA-12723 mRNA was highest 0.52 (0.40-0.64). Mycophenolic acid (OR: 1.42 [1.21-1.63]) and Belatacept (OR: 1.89 [1.3-2.49]) had highest risk for nonresponse. SOT had a parallelly decreased cellular response (ES: 0.42 [0.32-0.52]) in overall and control studies (OR: -3.12 [-0.4.12 to -2.13]).
INTERPRETATION
Overall, SOT develops a suboptimal response compared to the general population. Immunosuppression including mycophenolic acid, belatacept, and tacrolimus is associated with decreased response. Booster doses increase the immune response, but further upgradation in vaccination strategy for SOT is required.
Topics: Humans; Abatacept; COVID-19; COVID-19 Vaccines; Mycophenolic Acid; Organ Transplantation; Transplant Recipients
PubMed: 35924679
DOI: 10.1111/tid.13926 -
Journal of Clinical Rheumatology :... Mar 2023The aim of this study was to examine the effect and safety of biological agents for lupus nephritis (LN). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The aim of this study was to examine the effect and safety of biological agents for lupus nephritis (LN).
METHODS
PubMed, EMBASE, and the Cochrane Library databases were searched from their inception up to November 2021. The outcomes were overall response, complete remission, proteinuria, renal activity index, and adverse events (AEs). Only randomized controlled trials (RCTs) were included.
RESULTS
Nine RCTs (1645 patients) were included. The RCTs evaluated abatacept (n = 2), belimumab (n = 1), obinutuzumab (n = 1), atacicept (n = 1), IL-2 (n = 1), ocrelizumab (n = 1), and rituximab (n = 2). The use of biological agents was associated with higher likelihoods of achieving an overall response (relative risk [RR], 1.26; 95% confidence interval [CI], 1.15-1.39; p < 0.001; I2 = 14.3%; pQ = 0.301) and a complete response (RR, 1.33; 95% CI, 1.16-1.54; p < 0.001; I2 = 41.8%; pQ = 0.056). The use of biological agents was not associated with improvements in the urinary protein-to-creatinine ratio (weighted mean difference, 3.83; 95% CI, -3.71 to 11.38; p = 0.319; I2 = 99.4%; pQ < 0.001). The use of biological agents in patients with LN was also not associated with an increased risk of any AEs (RR, 1.01; 95% CI, 0.98-1.04; p = 0.519; I2 = 0.0%; pQ = 0.533), serious AEs (RR, 0.95; 95% CI, 0.82-1.09; p = 0.457; I2 = 0.0%; pQ = 0.667), grade >3 AEs (RR, 0.91; 95% CI, 0.67-1.22; p = 0.522; I2 = 0.0%; pQ = 0.977), infections (RR, 1.09; 95% CI, 0.99-1.20; p = 0.084; I2 = 0.0%; pQ = 0.430), and deaths (RR, 0.67; 95% CI, 0.36-1.24; p = 0.200; I2 = 0.0%; pQ = 0.439). The meta-regression analysis showed that follow-up duration and the sample size did not influence the complete response rate, whereas publications in 2012 to 2014 influence the rate compared with 2015 to 2020.
CONCLUSIONS
Biological agents seem to be effective and safe for managing patients with LN.
Topics: Humans; Abatacept; Lupus Nephritis; Rituximab; Biological Products; Randomized Controlled Trials as Topic
PubMed: 35699520
DOI: 10.1097/RHU.0000000000001877 -
RMD Open Mar 2022Randomised controlled trials (RCTs) have compared biological and targeted systemic disease-modifying antirheumatic drugs (DMARDS) against placebo in psoriatic arthritis... (Meta-Analysis)
Meta-Analysis
Targeted systemic therapies for psoriatic arthritis: a systematic review and comparative synthesis of short-term articular, dermatological, enthesitis and dactylitis outcomes.
INTRODUCTION
Randomised controlled trials (RCTs) have compared biological and targeted systemic disease-modifying antirheumatic drugs (DMARDS) against placebo in psoriatic arthritis (PsA); few have compared them head to head.
OBJECTIVES
To compare the efficacy and safety of all evaluated DMARDs for active PsA, with a special focus on biological DMARDs (bDMARDs) licensed for PsA or psoriasis.
METHODS
A systematic review identified RCTs and Bayesian network meta-analysis (NMA) compared treatments on efficacy (American College of Rheumatology (ACR) response, Psoriasis Area and Severity Index (PASI) response, resolution of enthesitis and dactylitis) and safety (patients discontinuing due to adverse events (DAE)) outcomes. Subgroup analyses explored ACR response among patients with and without prior biological therapy exposure.
RESULTS
The NMA included 46 studies. Results indicate that some tumour necrosis factor inhibitors (anti-TNFs) may perform numerically, but not significantly, better than interleukin (IL) inhibitors on ACR response but perform worse on PASI response. Few significant differences between bDMARDs on ACR response were observed after subgrouping for prior bDMARD exposure. Guselkumab and IL-17A or IL-17RA inhibitors-brodalumab, ixekizumab, secukinumab-were best on PASI response. These IL-inhibitors and adalimumab were similarly efficacious on resolution of enthesitis and dactylitis. Infliximab with and without methotrexate, certolizumab 400 mg every 4 weeks and tildrakizumab showed the highest rates of DAE; abatacept, golimumab and the IL-inhibitors, the lowest.
CONCLUSIONS
Despite similar efficacy for ACR response, IL-17A and IL-17RA inhibitors and guselkumab offered preferential efficacy to anti-TNFs in skin manifestations, and for enthesitis and dactylitis, thereby supporting drug selection based on predominant clinical phenotype.
Topics: Abatacept; Antirheumatic Agents; Arthritis, Psoriatic; Enthesopathy; Humans
PubMed: 35321874
DOI: 10.1136/rmdopen-2021-002074 -
Clinical and Experimental Rheumatology May 2022Due to the rarity of relapsing polychondritis (RP), no randomised clinical trial has been conducted to date and treatment remains empirical. We performed a systematic... (Review)
Review
OBJECTIVES
Due to the rarity of relapsing polychondritis (RP), no randomised clinical trial has been conducted to date and treatment remains empirical. We performed a systematic literature review to assess the efficacy of the main conventional immunosuppressants and biotherapies used in RP.
METHODS
We searched MEDLINE for original articles without language restriction. Abstracts from American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) were also considered for inclusion. Observational studies and clinical trials reporting on the efficacy of conventional immunosuppressants and biotherapies in adult patients with RP were selected and pooled response rates for each treatment were computed.
RESULTS
Of 304 articles and abstracts identified, 31 underwent full-text review, and 11 were included. The studies involved a total of 177 patients, exposed to a total of 247 lines of treatments. The main treatments studied (by number of lines) were: TNF inhibitors (TNFi), n=92; methotrexate (MTX), n=38; tocilizumab (TCZ), n=26; anakinra (ANA), n=21; rituximab (RTX), n=16; abatacept (ABT), n=14; cyclophosphamide (CYC), n=14; azathioprine (AZA), n=13. The pooled response rates across studies were: 72% [95% CI: 42-95] for ABT, 66% [95% CI: 49-82] for TCZ, 64% [95% CI: 53-74] for TNFi, 56% [95% CI: 37-73] for MTX, 47% [95% CI: 26-68] for ANA, 43% [95% CI: 20-68] for RTX. Based on more limited data, response rates for AZA and CYC ranged from 38 to 100% and from 25 to 100%, respectively.
CONCLUSIONS
In this systematic review of available evidence regarding the treatment of relapsing polychondritis, ABT, TCZ and TNFi were the drugs associated with the best outcomes. ABT efficacy must be interpreted in light of the small number of patients treated. While MTX had slightly less efficacy, it is one of the drugs for which data are the most robust.
Topics: Abatacept; Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Immunosuppressive Agents; Methotrexate; Polychondritis, Relapsing; Rituximab; Tumor Necrosis Factor Inhibitors
PubMed: 35238756
DOI: 10.55563/clinexprheumatol/h9gq1o -
Clinical and Experimental Rheumatology Feb 2022Juvenile idiopathic inflammatory myopathies (JIIMs) are a heterogeneous group of systemic autoimmune diseases. Juvenile dermatomyositis (JDM) is the predominant form of...
OBJECTIVES
Juvenile idiopathic inflammatory myopathies (JIIMs) are a heterogeneous group of systemic autoimmune diseases. Juvenile dermatomyositis (JDM) is the predominant form of JIIMs, and is a rare, chronic autoimmune illness characterised by symmetric, proximal muscle damages and involvement of the skin. In the last two decades, the use of monoclonal antibodies has also been expanded to JIIMs; however, there is limited evidence on use of these treatments. We assessed the efficacy/effectiveness and safety of biologic agents in JIIMs.
METHODS
A systematic literature review was conducted using Embase®, MEDLINE®, MEDLINE®-In Process and Cochrane library to identify studies on biologics agents in JIIMs published in English language as full-text articles (1975 to December 2020) or conference abstracts (2000 to December 2020). Databases were searched with the key words regarding chronic myositis crossed with "biologic agents OR tocilizumab OR rituximab OR adalimumab OR infliximab OR anti-TNF OR etanercept". Of note, we did not include children, age, or age limits in the search as medical subject headings terms because we may have been able to extract a sub cohort of children from studies including both children and adults.
RESULTS
Of the 1633 retrieved publications, 18 articles were identified for a total of 165 patients. In real-world studies, definition of complete (CR) or partial response (PR) varied. JIIMs patients were most often treated with anti-TNF (88 pts); patients received etanercept (ETA), 48 patients infliximab (IFX), 4 patients received adalimumab (ADA). In other 15 patients IFX was followed by ADA. Rituximab (RTX) was used in 73 children. A single case series reported the use of abatacept (ABA) in 4 patients. Despite the reduced number of treated patients, complete response on myositis was reported in 29.6% (8/26) patients treated with at least one anti-TNF and in 38% (10/26) treated by RTX. Complete response of skin vasculitis has been reached in 33% (4/12) children on anti-TNF and in 36% on RTX (21/58). Anti-TNF agents might be efficient in treating calcinosis lesions.
CONCLUSIONS
Currently, the available evidence regarding the use of biologic treatment in JIIMs results quite limited but suggest a promising the use of anti-TNF agents and RTX in treating active JIIMs. Anti-TNF treatment might have a role in treating calcinosis. However, an overall very low quality of the available studies and multiple confounding factors hamper to suggest a treatment over another. Thus, randomised clinical trials are urgently required to attempt the optimal treatment in real-world setting.
Topics: Adalimumab; Adult; Antirheumatic Agents; Biological Products; Biological Therapy; Child; Etanercept; Humans; Infliximab; Myositis; Precision Medicine; Tumor Necrosis Factor Inhibitors
PubMed: 34905479
DOI: 10.55563/clinexprheumatol/ltrj4l -
Reumatologia Clinica Nov 2021To review the available evidence on the impact of rheumatoid arthritis (RA) treatments in associated diffuse interstitial lung disease (ILD).
OBJECTIVE
To review the available evidence on the impact of rheumatoid arthritis (RA) treatments in associated diffuse interstitial lung disease (ILD).
METHODS
Systematic review of studies evaluating the impact of pharmacological treatment in patients with RA and ILD. A bibliographic search in MEDLINE, EMBASE and Cochrane, a selection of articles and the methodological quality assessment (FLC 3.0 OSTEBA) and grading of the level of evidence (SING) of the selected articles were performed.
RESULTS
1,720 references were identified in primary search and 7 in manual or indirect. Forty-three articles were included: 7 systematic reviews, 2 randomized clinical trials, 5 cohort studies, 8 case-control studies and 21 case series. Methotrexate (MTX) and leflunomide (LEF) do not increase incidence, complications or mortality due to ILD. Although the results are not uniform, anti-TNF have often had worse outcomes in incidence, progression and mortality due to ILD than MTX, LEF, abatacept (ABA) and rituximab (RTX). The evidence found is scarce for JAK kinase and antifibrotic inhibitors, and controversial for IL-6 inhibitors.
CONCLUSIONS
There is no evidence that MTX or LEF worsens the prognosis of patients with AR-EPID. RTX and ABA seem to have better results than other biologicals, such us TNFi, often achieving stabilization and, in some cases, the improvement of ILD in patients with RA.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Lung Diseases, Interstitial; Pharmaceutical Preparations; Tumor Necrosis Factor Inhibitors
PubMed: 34756311
DOI: 10.1016/j.reumae.2020.04.010