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Journal of Clinical Medicine Sep 2021Scleroderma (morphea) en coup de sabre is a localized subtype restricted to the frontoparietal region of the head. Current treatment paradigms rely on low levels of... (Review)
Review
Scleroderma (morphea) en coup de sabre is a localized subtype restricted to the frontoparietal region of the head. Current treatment paradigms rely on low levels of evidence, primarily case reports and case series-supported by expert opinions. The aim of this article was to systematically analyze current data related to the treatment of localized scleroderma en coup de sabre. The databases Scopus, PubMed, and EBSCO were searched for all reports discussing the treatment of localized scleroderma en coup de sabre. The keywords en coup de sabre, "facial linear scleroderma", and "morphea linearis", combined with "treatment" or "therapy" were used as search terms. A total of 34 articles analyzed treatment outcomes for patients with localized scleroderma en coup de sabre including 4 retrospective cohort studies, 2 prospective cohort studies, 4 case series, and 24 case reports, representing a total of 69 patients (38 children and 31 adults). Methotrexate was the most commonly investigated treatment (26 patients) with a highest response rate (26/26, 100%). Other treatments included systemic glucocorticosteroids (nine patients), followed by UVA1 (four patients), mycophenolate mofetil (two patients), hydroxychloroquine (five patients), abatacept (two patients), tocilizumab (three patients), cyclosporine (one patient), interferon gamma (one patient), PUVA therapy (two patients), NB-UVB therapy (one patient), and pulsed dye laser (one patient). Reconstructive and surgery treatment was successfully used for lesions with settled disease activity to improve the cosmetic aspect of the lesions. Conclusion: methotrexate is the most often-studied treatment and reported good clinical outcomes in children and adults with localized scleroderma en coup de sabre.
PubMed: 34640533
DOI: 10.3390/jcm10194517 -
Arthritis Care & Research Apr 2020We performed a systematic review and meta-analysis to evaluate the comparative effects of tumor necrosis factor inhibitors (TNFi), non-TNFi biologics, and conventional... (Meta-Analysis)
Meta-Analysis
Comparative Risk of Cardiovascular Events With Biologic and Synthetic Disease-Modifying Antirheumatic Drugs in Patients With Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.
OBJECTIVE
We performed a systematic review and meta-analysis to evaluate the comparative effects of tumor necrosis factor inhibitors (TNFi), non-TNFi biologics, and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on cardiovascular risk in rheumatoid arthritis (RA).
METHODS
Using a systematic search through May 8, 2018, we included 14 observational studies in adults with RA treated with TNFi, non-TNFi biologics, tofacitinib, or csDMARDs, reporting the risk of major adverse cardiovascular events (MACE) or stroke. Only studies reporting active comparators were included. We performed random effects meta-analysis and estimated odds ratios (ORs) and 95% confidence intervals (95% CIs).
RESULTS
As compared to TNFi, tocilizumab was associated with a decreased risk of MACE (OR 0.59 [95% CI 0.34-1.00]), whereas csDMARDs were associated with an increased risk of MACE (csDMARDs including methotrexate OR 1.45 [95% CI 1.09-1.93]; without methotrexate OR 2.57 [95% CI 1.32-5.00]), without heterogeneity (I = 0%); there was no difference in risk of MACE between abatacept and TNFi (OR 0.89 [95% CI 0.71-1.11]), or between tocilizumab and abatacept (OR 0.81 [0.57-1.16]). Based on 11 cohorts (n = 135,053 patients), as compared to TNFi, csDMARDs were associated with an increased risk of stroke (OR 1.17 [95% CI 1.01-1.36]); there was no difference in risk of stroke between different biologics (tocilizumab versus TNFi OR 0.98 [95% CI 0.59-1.61]; abatacept versus TNFi OR 1.08 [0.86-1.34]; tocilizumab versus abatacept OR 0.73 [95% CI 0.39-1.38]), without heterogeneity (I = 0%). No comparative studies on cardiovascular risk with tofacitinib were identified.
CONCLUSION
Based on meta-analysis, as compared to TNFi, tocilizumab may be associated with a reduced risk of MACE, whereas csDMARDs may be associated with an increased risk of MACE and stroke.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Cardiovascular Diseases; Humans; Risk
PubMed: 30875456
DOI: 10.1002/acr.23875 -
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 -
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 -
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 -
Deutsches Arzteblatt International Oct 2019Monoclonal antibodies (mAb) and fusion proteins (FP) are increasingly being used in children and adolescents. In this review, we analyze the evidence for their safety...
BACKGROUND
Monoclonal antibodies (mAb) and fusion proteins (FP) are increasingly being used in children and adolescents. In this review, we analyze the evidence for their safety and efficacy in the treatment of the most common chronic inflammatory diseases.
METHODS
We systematically searched PubMed, AWMF.org, and other databases for high-quality trials (i.e., randomized controlled trials with clinical primary endpoints) and guidelines published at any time up to 10 December 2018 that dealt with mAb and FP that are approved for pediatric use. The search term was "monoclonal anti- body/fusion protein [e. g. adalimumab] AND children."
RESULTS
The 620 hits included 25 high-quality trials (20 of them manufacturer- sponsored) on 9 mAb/FP (omalizumab, adalimumab, etanercept, ustekinumab, infliximab, golimumab, anakinra, canakinumab, tocilizumab, and abatacept), as well as 6 guidelines (3 each of levels S3 and S2k) on the treatment of bronchial asthma, psoriasis, juvenile idopathic arthritis, and chronic inflammatory bowel diseases. For none of these conditions are mAb and FP the drugs of first choice. Adverse drug effects are rare but sometimes severe (infection, immune dysregulation, tumors).
CONCLUSION
The retrieved trials have deficiencies that make it difficult to reliably evaluate the efficacy, safety, and utility of mAb/FP for children and adolescents with chronic inflammatory diseases. mAb/FP nonetheless represent a treatment option to be considered in case conventional immune-modulating drugs are ineffective. Researcher-initiated, high-quality trials and manufacturer-independent, systematic long-term evaluations of adverse effects (e.g., tumors) are sorely needed.
Topics: Adolescent; Antibodies, Monoclonal; Biological Products; Child; Humans; Proteins; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31711560
DOI: 10.3238/arztebl.2019.0703 -
Cureus Apr 2024Type 1 diabetes mellitus is an autoimmune condition characterized by insulin deficiency resulting from loss of function of beta cells in the pancreas, leading to... (Review)
Review
Type 1 diabetes mellitus is an autoimmune condition characterized by insulin deficiency resulting from loss of function of beta cells in the pancreas, leading to hyperglycemia and associated long-term systemic complications and even death. Immunotherapy demonstrates beta cell function-preserving potential; however, its impact on C-peptide levels, a definitive biomarker of beta cell function, and endogenous insulin secretion remain unclear. A systematic review of various immunotherapeutic interventions is hence needed for a comprehensive assessment of their effectiveness as well as identifying research gaps and influencing future research and clinical decisions. An extensive literature search was done in PubMed, Scopus, and Cochrane Library databases using precise keywords and filters to identify relevant studies. Three independent reviewers assessed eligibility according to predetermined eligibility criteria, and data was extracted. The Cochrane risk of bias assessment tool (RoB 2.0) was used to evaluate the quality and validity of the included studies. A senior reviewer resolved discrepancies and differences of opinion between independent reviewers. A total of 11 studies were included, with 1464 study participants. Both Phase II and III trials were included. Within the included studies, four studies assessed the anti-CD3 monoclonal antibody otelixizumab as an intervention. Another anti-CD3 monoclonal antibody, teplizumab, was assessed as an intervention in four studies, whereas two studies assessed the anti-CD20 antibody rituximab and one study assessed abatacept as its interventional drug. Otelixizumab demonstrated benefits at higher doses but was associated with adverse effects like Ebstein-Barr virus reactivation and cytomegalovirus infection, while at lower doses it failed to show a significant difference in C-peptide levels or glycosylated hemoglobin (HbA1c). Teplizumab, on the other hand, showed promise in reducing C-peptide loss and exogenous insulin requirements and was associated with adverse events such as rash, lymphopenia, urinary tract infection, and cytokine release syndrome. However, these reactions were only associated with therapy initiation, and they subsided on their own. Rituximab improved C-peptide responses, and abatacept therapy demonstrated reduced loss of C-peptide, improved C-peptide levels, and lowered HbA1c. Teplizumab, rituximab, otelixizumab, and abatacept show potential for preserving beta cell function by reducing C-peptide loss in patients with type I diabetes mellitus. However, careful monitoring of adverse reactions, particularly viral infections and cytokine release syndrome, is necessary for the safe implementation of these therapies.
PubMed: 38800168
DOI: 10.7759/cureus.58981 -
Reumatologia Clinica Jun 2020To 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 as anti-TNF, often achieving stabilization and, in some cases, the improvement of ILD in patients with RA.
PubMed: 32571732
DOI: 10.1016/j.reuma.2020.04.015 -
Arthritis Research & Therapy Jun 2021New molecular mechanisms that can be targeted with specific drugs have recently emerged for the treatment of systemic sclerosis (SSc) patients. Over the past 3 years,... (Review)
Review
New molecular mechanisms that can be targeted with specific drugs have recently emerged for the treatment of systemic sclerosis (SSc) patients. Over the past 3 years, the achievement of one large phase 3 trial has led to the approval by drug agencies of the first drug licenced for SSc-related interstitial lung disease. Given this exciting time in the SSc field, we aimed to perform a systemic literature review of phase 1, phase 2 and phase 3 clinical trials and large observational studies about targeted therapies in SSc. We searched MEDLINE/PubMed, EMBASE, and ClinicalTrials.gov for clinical studies from 2016 with targeted therapies as the primary treatment in patients with SSc for skin or lung involvement as the primary clinical outcome measure. Details on the study characteristics, the trial drug used, the molecular target engaged by the trial drug, the inclusion criteria of the study, the treatment dose, the possibility of concomitant immunosuppression, the endpoints of the study, the duration of the study and the results obtained were reviewed. Of the 973 references identified, 21 (4 conference abstracts and 17 articles) were included in the systematic review. A total of 15 phase 1/phase 2 clinical trials, 2 phase 3 clinical trials and 2 observation studies were analysed. The drugs studied in phase 1/phase 2 studies included the following: inebilizumab, dabigatran, C-82, pomalidomide, rilonacept, romilkimab, tocilizumab, tofacitinib, pirfenidone, lenabasum, abatacept, belimumab, riociguat, SAR100842 and lanifibranor. All but 3 studies were performed in early diffuse SSc patients with different inclusion criteria, while 3 studies were performed in SSc patients with interstitial lung disease (ILD). Phase 3 clinical trials investigated nintedanib and tocilizumab. Nintedanib was investigated in SSc-ILD patients whereas tocilizumab focused on early diffuse SSc patients with inflammatory features. Two observational studies including > 50 patients with rituximab as the targeted drug were also evaluated. All these studies offer a real hope for SSc patients. The future challenges will be to customize patient-specific therapeutics with the goal to develop precision medicine for SSc.
Topics: Humans; Lung Diseases, Interstitial; Scleroderma, Diffuse; Scleroderma, Systemic
PubMed: 34074331
DOI: 10.1186/s13075-021-02536-5 -
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