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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 Investigative Dermatology Oct 2021The effect of biologics on the risk for cardiovascular disease in patients with psoriasis is still unclear despite their widespread use. (Meta-Analysis)
Meta-Analysis
Impact of Biological Agents on Imaging and Biomarkers of Cardiovascular Disease in Patients with Psoriasis: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.
BACKGROUND
The effect of biologics on the risk for cardiovascular disease in patients with psoriasis is still unclear despite their widespread use.
OBJECTIVE
The objective of this study was to examine the impact of licensed biological therapies on imaging and biomarkers of cardiovascular disease risk in patients with psoriasis by a systematic review and meta-analysis of placebo-controlled trials.
METHODS
A comprehensive search of studies published before 1 June 2020 was performed in Medline-Ovid, EMBASE, and CENTRAL using a predefined strategy to identify relevant articles.
RESULTS
Five studies were included for the final examination, and two studies were included in the meta-analysis. We did not find a significant reduction in aortic vascular inflammation in patients treated with adalimumab compared with those who received placebo at weeks 12-16. There was no beneficial effect on imaging biomarkers (aortic vascular inflammation or flow-mediated dilatation) of cardiovascular disease risk in patients exposed to biological therapies (adalimumab and secukinumab) compared with those exposed to placebo, except for ustekinumab showing a reduction in aortic vascular inflammation at week 12 but not at week 52 after the open-label extension period. The strongest reduction in blood-based cardiometabolic risk biomarkers was observed with adalimumab (CRP, TNF-α, IL-6, and GlycA) and phototherapy (CRP and IL-6) compared with that observed with placebo.
CONCLUSIONS
Randomized controlled trials show that ustekinumab reduces aortic vascular inflammation and that TNF-α inhibitors and phototherapy reduce CRP and IL-6. These surrogate marker findings require randomized controlled trials evaluating cardiovascular events to inform clinical practice.
Topics: Adalimumab; Biological Factors; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Humans; Interleukin-6; Psoriasis; Tumor Necrosis Factor-alpha
PubMed: 33891953
DOI: 10.1016/j.jid.2021.03.024 -
Drugs in Context 2022Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with a significant negative impact on the quality of life of patients. (Review)
Review
BACKGROUND
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with a significant negative impact on the quality of life of patients.
METHODS
We conducted a systematic review to assess current treatment for HS, with a special focus on therapies approved or used in Brazil. We used the PICO framework to improve the research process. The systematic review was reported in line with the PRISMA statement checklist. The search was conducted with clinical questions on two global databases (PubMed (MEDLINE) and Google Scholar) and three databases especially selected to retrieve Brazilian outcomes (BVS, SCIELO and REDALYC).
RESULTS
Overall, 4640 articles were screened, 182 articles were analysed and 70 were used in a thematic qualitative analysis. Of these, 12 articles were from Brazil. The evidence-based literature was largely limited to case reports, case series, observational studies and expert opinion. Topical therapy, lifestyle interventions and oral antibiotics appeared as effective measures for mild HS. However, moderate-to-severe HS remains refractory to conventional treatments.
CONCLUSION
Some biologic agents, such as adalimumab, infliximab, ustekinumab and secukinumab, have been shown to be effective in the management of moderate-to-severe HS that failed conventional treatment and demonstrated a good tolerability and safety profile.
PubMed: 35145556
DOI: 10.7573/dic.2021-9-6 -
Clinical Ophthalmology (Auckland, N.Z.) 2021Noninfectious pediatric uveitis is a potentially blinding disease often associated with systemic conditions. In cases of chronic anterior uveitis without adequate... (Review)
Review
PURPOSE
Noninfectious pediatric uveitis is a potentially blinding disease often associated with systemic conditions. In cases of chronic anterior uveitis without adequate response to steroids and immunosuppressants, biological response modifiers would be viable therapeutic options. Still, evidence is lacking on the safety of the long-term use of these drugs in children. Therefore, this study aimed to evaluate the efficacy and safety of biological therapy to treat noninfectious pediatric uveitis.
METHODS
A systematic review was performed to identify original studies involving biological therapy for children diagnosed with noninfectious uveitis. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) classification system.
RESULTS
Nine studies involving 526 children were eligible. Adalimumab was superior to placebo in reducing inflammatory activity (risk ratio (RR) 3.21 [95% confidence interval (CI) 1.65-6.27]; P = 0.0006; I = 0%) and steroid use (RR 2.27 [95% CI 1.03-4.99]; P = 0.04; I = 0%, low-certainty evidence). There was no difference between adalimumab and placebo in the occurrence of systemic adverse events (RR 2.51 [95% CI 0.74-8.54]; P = 0.14; I = 48%) and local events (RR 1.15 [95% CI 0.46-2.88]; P= 0.76; I = 1%). There was no difference between adalimumab and infliximab in response to treatment (RR 1.18 [95% CI 0.69-2.03]; P= 0.55; I = 91%, very low-certainty evidence) and in the occurrence of adverse effects (RR 0.84 [95% CI 0.41-1.73]; P= 0.64; I = 18%, low-certainty evidence).
CONCLUSION
There is low to very-low evidence that biological therapy is effective and safe in managing noninfectious pediatric uveitis. Future large randomized trials may provide more substantial evidence to confirm these results.
PubMed: 34522080
DOI: 10.2147/OPTH.S322445 -
Rheumatology and Therapy Mar 2021Although treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) has significantly improved clinical outcomes in patients with rheumatoid arthritis (RA),... (Review)
Review
Although treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) has significantly improved clinical outcomes in patients with rheumatoid arthritis (RA), many patients do not have access to these treatments. As cost-effective alternatives to their reference products (RPs), biosimilars provide an opportunity to increase access to bDMARDs. The European Medicines Agency and the US Food and Drug Administration have detailed pathways for the approval of biosimilars based on establishing the similarity of the biosimilar to the RP in terms of structure and function, pharmacokinetics (PK), efficacy, safety, and immunogenicity. A number of biosimilars of adalimumab, infliximab, etanercept, and rituximab RPs have been approved in the United States and/or European Union. This article is focused on the seven adalimumab biosimilars. A review of the data for the biosimilars FKB327, ABP 501, BI 695501, GP2017, MSB11022, PF-06410293, and SB5 confirm that these products are highly similar to the adalimumab RP with regard to structure, physicochemical and biological properties, PK, safety, immunogenicity, and efficacy in the treatment of RA and other chronic immune-mediated, inflammatory conditions. Data from several switching studies showed no changes in efficacy, safety, trough serum drug concentration, or immunogenicity between the biosimilars and their RP.Trial registration: ClinicalTrials.gov identifiers: NCT02260791, NCT02405780, NCT01970475, NCT02137226, NCT02045979, NCT02744755, NCT02144714, NCT02167139, NCT03014947, NCT02114931, NCT02640612, NCT02167139, NCT03052322, NCT02480153. EudraCT numbers: 2012-005140-23, 2012-000785-37, 2013-003722-84, 2015-000579-28, 2014-002879-29, 2014-000662-21, 2013-004654-13, 2015-002634-41, 2014-005229-11, 2016-002852-26, 2014-000352-29.
PubMed: 33263165
DOI: 10.1007/s40744-020-00259-8 -
Hepatology Communications Jan 2024Primary sclerosing cholangitis (PSC) is an immune-mediated, chronic cholestatic liver disease. Currently, liver transplantation is the only established life-saving... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Primary sclerosing cholangitis (PSC) is an immune-mediated, chronic cholestatic liver disease. Currently, liver transplantation is the only established life-saving treatment. Several studies have evaluated the effect of different biologic therapies on PSC with inconclusive findings. We conducted a systematic review and meta-analysis to assess the effects of biologics in PSC and associated inflammatory bowel disease (IBD).
METHODS
MEDLINE, Scopus, and Embase were searched up to July 31, 2023, for studies reporting the effects of biologics in patients with PSC-IBD. Effects of biologic therapy on alkaline phosphatase, total bilirubin, ulcerative colitis response score, and adverse events were calculated and expressed as standardized difference of means (SMD), proportions, and 95% CI using a random-effects model.
RESULTS
Six studies, including 411 PSC-IBD patients who received biologics, were included. Biologic treatment was associated with no change in alkaline phosphatase (SMD: 0.1, 95% CI: -0.07 -0.17, p=0.43), but a small and statistically significant increase in total bilirubin (SMD: 0.2, 95% CI: 0.05-0.35, p<0.01). 31.2% (95% CI: 23.8-39.7) of patients with IBD achieved endoscopic response, and there was a significant improvement in ulcerative colitis response score (SMD: -0.6,95% CI: -0.88 to 0.36, p<0.01). Furthermore, 17.6% (95% CI: 13.0-23.5) of patients experienced adverse events severe enough to discontinue therapy, and 29.9% (95% CI: 25.2-34.8) had a loss of response to biologics.
CONCLUSIONS
Treatment of patients with PSC-IBD with biologics (vedolizumab, infliximab, and adalimumab) was not associated with improvement of biochemical markers of cholestasis. Biologics are effective in treating the colitis associated with PSC. Vedolizumab was associated with worsening liver enzymes in contrast to other biologics, a finding that warrants further study.
Topics: Humans; Colitis, Ulcerative; Alkaline Phosphatase; Cholangitis, Sclerosing; Inflammatory Bowel Diseases; Bilirubin; Cholestasis; Biological Products
PubMed: 38206197
DOI: 10.1097/HC9.0000000000000347 -
Medicine Jun 2021Adalimumab is used as a first-line biologic agent in the management of moderate-to-severe hidradenitis suppurativa (HS). The objective of the present study was to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adalimumab is used as a first-line biologic agent in the management of moderate-to-severe hidradenitis suppurativa (HS). The objective of the present study was to evaluate the efficacy and safety of adalimumab in patients with moderate-to-severe HS.
METHODS
We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. Pooled estimates, namely standardized mean difference (SMD) and relative risk (RR), were calculated using random-effect model with trial sequential analysis. Small study effects were examined using the Doi plot. Certainty of evidence (CoE) was assessed using "The Grading of Recommendations Assessment, Development, and Evaluation" approach, and number-needed-to-treat (NNT) was calculated.
RESULTS
Five randomized controlled trials, involving 1014 patients, were included. We performed subgroup analysis of adalimumab administered subcutaneously both weekly and every other week. Adalimumab administered weekly was associated with better clinical response achievement (RR 1.76, 95% confidence interval [95% CI] 1.35-2.29; trial sequential analysis TSA-adjusted CI 1.01-3.08; CoE: low; NNT = 5) and a significant improvement in modified Sartorius score (SMD = -0.45, 95% CI = -0.76 to -0.13; CoE: very low; NNT = 10) and dermatology life quality index (DLQI) (SMD -0.47, 95% CI -0.61 to -0.32; CoE: low; NNT = 10). Nevertheless, adalimumab administered every other week showed an improvement only in modified Sartorius score. The pooled RRs of adverse events in both groups revealed no statistical significance when compared with the placebo.
CONCLUSIONS
Adalimumab administered weekly resulted in not only better clinical responses than placebo but also significantly improved disease severity and quality of life of patients with moderate-to-severe HS. Our study provides supporting evidence to the current guidelines and aids decision-making in the application of adalimumab in HS management.
Topics: Adalimumab; Adult; Antibodies, Monoclonal, Humanized; Case-Control Studies; Hidradenitis Suppurativa; Humans; Injections, Subcutaneous; Middle Aged; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha
PubMed: 34087885
DOI: 10.1097/MD.0000000000026190 -
Cureus Sep 2023The widely accepted standard of care for chronic cutaneous sarcoidosis is corticosteroids. However, when this treatment is shown to be refractory, other interventions... (Review)
Review
Recent Clinical Studies on the Effects of Tumor Necrosis Factor-Alpha (TNF-α) and Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) Antibody Therapies in Refractory Cutaneous Sarcoidosis: A Systematic Review.
The widely accepted standard of care for chronic cutaneous sarcoidosis is corticosteroids. However, when this treatment is shown to be refractory, other interventions must be considered. In this review, we report the current progress of clinical studies on various monoclonal antibody therapies and their future potential as primary interventions for refractory cutaneous sarcoidosis. In this systematic review, clinical studies on the management of refractory cutaneous sarcoidosis were retrieved from PubMed and ScienceDirect databases. Studies were screened based on article type, publication within the last 10 years, and access to free full text. The articles selected consisted of case studies, clinical trials, and observational studies. The studies needed to focus on cases of diagnosed cutaneous sarcoidosis at the time of the study and involve adult patients resistant to corticosteroid regimens, with or without additional immunomodulators. Only interventions that included tumor necrosis factor-alpha (TNF-α) (e.g., infliximab and adalimumab) or Janus kinase/signal transducers and activators of transcription (JAK/STAT) (e.g., ruxolitinib and tofacitinib) antibody therapy were considered. Two authors independently conducted quality assessments using the Joanna Briggs Institute Critical Appraisal and NIH Study Quality Assessment tools. A total of 16 clinical studies were included in this systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. Of the 16 cases included, 15 studies demonstrated partial to complete resolution of cutaneous lesions within a range of two weeks to 18 months from initiation of antibody therapy. Studies on anti-TNF-α intervention demonstrated the most adverse events, including two deaths and one case associated with cutaneous exacerbation. Studies on anti-JAK-STAT interventions demonstrate no adverse events after treatment; however, patient study size was limiting. Recent studies have shown promising potential for anti-TNF-α and anti-JAK-STAT inhibitors to become the mainstay interventions in refractory cutaneous sarcoidosis. Due to limited population studies, the current data on the efficacy and safety of antibody therapies have not yielded a standardized FDA-approved steroid-sparing treatment. Therefore, a need for more population studies on the effectiveness of third-line intervention in refractory cutaneous sarcoidosis is necessary.
PubMed: 37818515
DOI: 10.7759/cureus.44901 -
The Cochrane Database of Systematic... Oct 2022Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA) and a potentially sight-threatening condition characterized by... (Review)
Review
BACKGROUND
Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA) and a potentially sight-threatening condition characterized by intraocular inflammation. Current treatment for JIA-associated uveitis (JIA-U) is largely based on physician experience, observational evidence and consensus guidelines, resulting in considerable variations in practice. OBJECTIVES: To evaluate the effectiveness and safety of tumor necrosis factor (TNF) inhibitors used for treatment of JIA-U.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We last searched the electronic databases on 3 February 2022.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing TNF inhibitors with placebo in participants with a diagnosis of JIA and uveitis who were aged 2 to 18 years old.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology and graded the certainty of the body of evidence for seven outcomes using the GRADE classification.
MAIN RESULTS
We included three RCTs with 134 participants. One study conducted in the USA randomized participants to etanercept or placebo (N = 12). Two studies, one conducted in the UK (N = 90) and one in France (N = 32), randomized participants to adalimumab or placebo. All studies were at low risk of bias. Initial pooled estimates suggested that TNF-inhibitors may result in little to no difference on treatment success defined as 0 to trace cells on Standardization of Uveitis Nomenclature (SUN)-grading; or two-step decrease in activity based on SUN grading (estimated risk ratio (RR) 0.66; 95% confidence interval (CI) 0.21 to 2.10; 2 studies; 43 participants; low-certainty evidence) or treatment failure defined as a two-step increase in activity based on SUN grading (RR 0.31; 95% CI 0.01 to 7.15; 1 study; 31 participants; low-certainty evidence). Further analysis using the individual trial definitions of treatment response and failure suggested a positive treatment effect of TNF inhibitors; a RR of treatment success of 2.60 (95% CI 1.30 to 5.20; 3 studies; 124 participants; low-certainty evidence), and RR of treatment failure of 0.23 (95% CI 0.11 to 0.50; 3 studies; 133 participants). Almost all the evidence was on adalimumab and the evidence on etanercept was very limited. For secondary outcomes, one study suggests that adalimumab may have little to no effect on risk of recurrence after induction of remission at three months (RR 2.50, 95% CI 0.31 to 20.45; 90 participants; very low-certainty evidence) and visual acuity, but the evidence is very uncertain; mean difference in longitudinal logMAR score change over six months was -0.01 (95% CI -0.06 to 0.03) and -0.02 (95% CI -0.07 to 0.03) using the best and worst logMAR measurement, respectively (low-certainty evidence). Low-certainty evidence from one study suggested that adalimumab treatment results in reduction of topical steroid doses at six months (hazard ratio 3.58; 95% CI 1.24 to 10.32; 74 participants who took one or more topical steroid per day at baseline). Adverse events, including injection site reactions and infections, were more common in the TNF inhibitor group. Serious adverse events were uncommon.
AUTHORS' CONCLUSIONS
Adalimumab appears to increase the likelihood of treatment success and decrease the likelihood of treatment failure when compared with placebo. The evidence was less conclusive about a positive treatment effect with etanercept. Adverse events from JIA-U trials are in keeping with the known side effect profile of TNF inhibitors. Standard validated JIA-U outcome measures are required to homogenize assessment and to allow for comparison and analysis of multiple datasets.
Topics: Adalimumab; Adolescent; Arthritis, Juvenile; Child; Child, Preschool; Etanercept; Humans; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Uveitis
PubMed: 36239193
DOI: 10.1002/14651858.CD013818.pub2 -
Journal of Translational Autoimmunity 2020In the last decade, new scientific findings significantly improved our understanding of the molecular pathogenesis of autoinflammation and have resulted in the... (Review)
Review
In the last decade, new scientific findings significantly improved our understanding of the molecular pathogenesis of autoinflammation and have resulted in the identification and definition of several pyoderma gangrenosum-associated autoinflammatory syndromes (PGAAIS) as new and distinct clinical entities. These different clinical entities include PAPA (pyogenic arthritis, pyoderma gangrenosum and acne conglobata), PASH (pyoderma gangrenosum, acne and suppurative hidradenitis), PAPASH (pyoderma gangrenosum, acne, suppurative hidradenitis and pyogenic arthritis), PsAPASH (pyoderma gangrenosum, acne, suppurative hidradenitis and psoriatic arthritis), PASS (pyoderma gangrenosum, acne conglobata, suppurative hidradenitis, and axial spondyloarthritis) and PAC (pyoderma gangrenosum, acne and ulcerative colitis), which can be distinguished by their clinical presentation and the presence or absence of mutations in several genes, such as the genes encoding proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1), nicastrin (NCSTN), Mediterranean fever (MEFV) and nucleotide-binding oligomerization domain-containing protein (NOD). In this systematic review, we summarize the present knowledge of this rapidly developing hot topic and provide a guide to enable the easy diagnosis of these syndromes in everyday clinical practice. Moreover, we report a rare case of PASS syndrome demonstrating successful treatment with adalimumab and another case of a previously unreported combination of symptoms, including psoriatic arthritis, pyoderma gangrenosum, suppurative hidradenitis and Crohn's disease (newly coined PsAPSC), as examples. Because of the identification of similar genetic and pathogenic mechanisms of PGAAIS, we think the wide variety of seemingly different syndromes may represent distinct phenotypes of one disease.
PubMed: 33305249
DOI: 10.1016/j.jtauto.2020.100071