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Amara S, Pasumarthi A, Parikh N, Kodali N, Lebwohl M, Monks G. Psoriasis management tree based on comorbidity. Int J Dermatol 2025; 64:229-245. [PMID: 39420121 DOI: 10.1111/ijd.17497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Revised: 09/03/2024] [Accepted: 09/06/2024] [Indexed: 10/19/2024]
Abstract
Psoriasis, a common chronic inflammatory skin disorder, encompasses various subtypes, including guttate, pustular, erythrodermic, and the most common type, plaque psoriasis. Irrespective of the subtype, psoriasis can manifest with multisystemic presentations, including psoriatic arthritis, metabolic disorders, cardiovascular disease, malignancies, chronic kidney disease (CKD), psychiatric illness, and inflammatory bowel disease (IBD). Many comorbidities and concomitant conditions must be considered when selecting the most appropriate therapy for a patient (Kaushik et al., 2019 and Monks et al., 2021) . Ongoing clinical trials and the development of new therapeutic targets contribute to the continuous improvement of available treatment options. Given the dynamic landscape of therapies, particularly when managing complex patients with multiple comorbidities, dermatologists are constantly challenged with the task of adeptly tailoring treatments to each psoriasis patient. This article systematically reviews the current evidence, presenting it as an updated Psoriasis Decision Tree to assist physicians in selecting tailored treatment options.
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Affiliation(s)
- Shivkar Amara
- The Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Anusha Pasumarthi
- The Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Neil Parikh
- Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
| | | | - Mark Lebwohl
- The Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - George Monks
- Department of Dermatology, University of Oklahoma College of Medicine in Oklahoma City, Oklahoma, USA
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Mavrogeni S, Sapountzi E, Chiotopoulou K, Fotis L. New onset heart failure in adolescents with inflammatory joint disease treated with TNF-α inhibitors: a case-based review. Rheumatol Int 2024; 45:4. [PMID: 39692771 DOI: 10.1007/s00296-024-05750-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 12/06/2024] [Indexed: 12/19/2024]
Abstract
The safety of tumor necrosis factor (TNF) inhibitors has been demonstrated for over two decades. However, their effects on cardiovascular function in patients with rheumatic diseases remain controversial, and conclusions are additionally hampered by the cardiovascular complications inherent in such diseases. We present two 15-year-old patients diagnosed with ankylosing spondylitis and juvenile idiopathic arthritis classified as polyarthritis with positive rheumatoid factor, respectively. Soon after treatment onset with adalimumab and etanercept, respectively, they developed myocardial inflammation leading to heart failure. Their condition improved upon treatment discontinuation and onset of secukinumab and tocilizumab, respectively. A thorough literature search revealed that these are the only cases of heart failure reported to date after anti-TNF treatment in adolescents with rheumatic diseases. Although cardiovascular adverse effects seem to be very rare in this population, even atypical symptoms of cardiac failure should not be ignored, and cardiac function should be closely monitored when administering anti-TNF-α.
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Affiliation(s)
| | - Evdoxia Sapountzi
- 2nd Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA General Hospital, Thessaloniki, Greece
| | - Kyveli Chiotopoulou
- Division of Pediatric Rheumatology, Department of Pediatrics, Attikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Lampros Fotis
- Division of Pediatric Rheumatology, Department of Pediatrics, Attikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
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Tan S, Qi C, Zeng H, Wei Q, Huang Q, Pu X, Li W, Li Y, Tian P. Steroid-Refractory Myocarditis Induced by Immune Checkpoint Inhibitor Responded to Infliximab: Report of Two Cases and Literature Review. Cardiovasc Toxicol 2024; 24:1174-1191. [PMID: 39256296 PMCID: PMC11445312 DOI: 10.1007/s12012-024-09918-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 09/02/2024] [Indexed: 09/12/2024]
Abstract
Immune checkpoint inhibitors (ICIs), including anti-programmed cell death protein 1 and its ligand (PD-1/PD-L1) as well as anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4), have been widely used for treating solid tumors. Myocarditis is a potentially lethal immune-related adverse events (irAEs) caused by ICIs therapy. The treatment of steroid-refractory myocarditis is challenging. We reported two non-small-cell lung cancer patients with steroid-refractory myocarditis induced by ICI. The symptoms were not resolved after pulse corticosteroid therapy and subsequent treatment including intravenous immunoglobulin and mycophenolate mofetil. Considering the level of serum interleukin (IL)-6 decreased by > 50% and level of serum tumor necrosis factor-α (TNF-α) increased during the course of the disease, infliximab was used. Myocarditis gradually alleviated after infliximab treatment. The cases revealed that specific cytokine inhibitors have promising roles in the treatment of steroid-refractory myocarditis. Infliximab could be considered for patients with low level of IL-6 and elevated level of TNF-α.
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Affiliation(s)
- Sihan Tan
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, Sichuan, China
| | - Chang Qi
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, Sichuan, China
| | - Hao Zeng
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, Sichuan, China
| | - Qi Wei
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, Sichuan, China
| | - Qin Huang
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, Sichuan, China
| | - Xin Pu
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, Sichuan, China
| | - Weimin Li
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yalun Li
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
- Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, Sichuan, China.
| | - Panwen Tian
- Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
- Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, Sichuan, China.
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Jiang Y, Chen Y, Yu Q, Shi Y. Biologic and Small-Molecule Therapies for Moderate-to-Severe Psoriasis: Focus on Psoriasis Comorbidities. BioDrugs 2023; 37:35-55. [PMID: 36592323 PMCID: PMC9837020 DOI: 10.1007/s40259-022-00569-z] [Citation(s) in RCA: 41] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/14/2022] [Indexed: 01/03/2023]
Abstract
Psoriasis is a systemic immune-mediated disease associated with an increased risk of comorbidities, such as psoriatic arthritis, cardiovascular disease, metabolic syndrome, inflammatory bowel disease, psychiatric disorders, and malignancy. In recent years, with the advent of biological agents, the efficacy and safety of psoriasis treatments have dramatically improved. Presently, tumor necrosis factor-α inhibitors, interleukin-17 inhibitors, interleukin-12/23 inhibitors, and interleukin-23 inhibitors are approved to treat moderate-to-severe psoriasis. Small-molecule inhibitors, such as apremilast and deucravacitinib, are also approved for the treatment of psoriasis. Although it is still unclear, systemic agents used to treat psoriasis also have a significant impact on its comorbidities by altering the systemic inflammatory state. Data from clinical trials and studies on the safety and efficacy of biologics and small-molecule inhibitors provide important information for the personalized care and treatment for patients with psoriasis. Notably, treatment with interleukin-17 inhibitors is associated with new-onset or exacerbations of inflammatory bowel disease. In addition, great caution needs to be taken when using tumor necrosis factor-α inhibitors in patients with psoriasis with concomitant congestive heart failure, multiple sclerosis, and malignancy. Apremilast may induce weight loss as an adverse effect, presenting also with some beneficial metabolic actions. A better understanding of the characteristics of biologics and small-molecule inhibitors in the treatment of psoriasis comorbidities can provide more definitive guidance for patients with distinct comorbidities.
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Affiliation(s)
- Yuxiong Jiang
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China
| | - Youdong Chen
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China
| | - Qian Yu
- Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China.
| | - Yuling Shi
- Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China.
- Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China.
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Piaserico S, Messina F. Pharmacological management of severe plaque psoriasis in patients with cardiovascular disease. Expert Opin Pharmacother 2022; 23:853-864. [PMID: 35361040 DOI: 10.1080/14656566.2022.2060739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION There is compelling evidence about the independent association between psoriasis and an increased risk of cardiovascular diseases, in particular myocardial infarction, chronic heart failure and cardiac arrythmia. This is due to both the higher prevalence of traditional cardiovascular risk factors (including hypertension, diabetes, hyperlipidemia, obesity, and smoking) and an independent contribution of chronic systemic inflammation associated with psoriasis. Inflammation is not only important in atherosclerosis, but also is increasingly recognized as a contributing factor to heart failure and arrythmia through microvascular dysfunction and myocardial fibrosis. When treating a patient with severe psoriasis, it is recommended to take into consideration this enhanced cardiovascular risk. Moreover, the use of a systemic treatment in a patient with already existing cardiovascular comorbidities should always be considered with caution, assessing the pro and cons of these drugs. AREAS COVERED Herein, the authors review the pharmacological management of severe plaque psoriasis in patients with cardiovascular disease, providing their expert opinion and future perspectives on the subject. EXPERT OPINION Theoretically, anti-inflammatory drugs may not only dampen the systemic burden associated with psoriasis, but also potentially contribute to prevent long-term cardiovascular events in psoriasis. On the other hand, some treatments may also induce negative effects on the cardiovascular system. Whether findings from observational studies or ones evaluating surrogates of cardiovascular risk translate into reductions in cardiovascular events needs to be investigated by long-term clinical trials with clinically meaningful endpoints.
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Affiliation(s)
- Stefano Piaserico
- Department of Medicine, Dermatology Unit, University of Padua, Padua, Italy
| | - Francesco Messina
- Department of Medicine, Dermatology Unit, University of Padua, Padua, Italy
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Busaleh F, Albaqshi H, AlSultan S, Alateeq S, Alhashim LA, Aldandan Z, Alfarhan N. Dilated Cardiomyopathy in Pediatric Crohn's Patient: Is It a Manifestation or Consequence of Therapy? Cureus 2021; 13:e19357. [PMID: 34925971 PMCID: PMC8654073 DOI: 10.7759/cureus.19357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/08/2021] [Indexed: 11/05/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a debilitating chronic disorder that is classified into Crohn's disease, ulcerative colitis, and unspecified which are marked by recurrent gastrointestinal inflammatory episodes. Anti-tumor necrosis agents, especially infliximab, are considered the cornerstone in disease management. However, rare but serious adverse effects related to infliximab have been reported. Limited studies reported cardiac adverse effects as a result of using infliximab in IBD especially in the pediatric age group. Here, we report a case of an 11-year-old boy known to have Crohn's disease, who was on a regular infusion of infliximab at a monthly basis which developed dilated cardiomyopathy with severe depression of myocardial function.
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Affiliation(s)
- Fadi Busaleh
- Pediatric, Maternity and Children Hospital, Al-Ahsa, SAU
| | | | | | - Sarah Alateeq
- Pediatrics, College of Medicine, King Faisal University, Al-Ahsa, SAU
| | | | | | - Nawal Alfarhan
- Pediatric Gastroenterology, Maternity and Children Hospital, Al-Ahsa, SAU
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Cautela J, Zeriouh S, Gaubert M, Bonello L, Laine M, Peyrol M, Paganelli F, Lalevee N, Barlesi F, Thuny F. Intensified immunosuppressive therapy in patients with immune checkpoint inhibitor-induced myocarditis. J Immunother Cancer 2020; 8:jitc-2020-001887. [PMID: 33298621 PMCID: PMC7725077 DOI: 10.1136/jitc-2020-001887] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/20/2020] [Indexed: 12/14/2022] Open
Abstract
Background Myocarditis is a rare but life-threatening adverse event of cancer treatments with immune checkpoint inhibitors (ICIs). Recent guidelines recommend the use of high doses of corticosteroids as a first-line treatment, followed by intensified immunosuppressive therapy (IIST) in the case of unfavorable evolution. However, this strategy is empirical, and no studies have specifically addressed this issue. Therefore, we aimed to investigate and compare the clinical course, management and outcome of ICI-induced myocarditis patients requiring or not requiring IIST. Methods This case–control study included all patients consecutively admitted to The Mediterranean University Center of Cardio-Oncology (Aix-Marseille University, France) for the diagnosis of ICI-induced myocarditis according to Bonaca’s criteria and treated with or without IIST. In addition, we searched PubMed and included patients from previously published case reports treated with IIST in the analysis. The clinical, biological, imaging, treatment, all-cause death and cardiovascular death data of patients who required IIST were compared with those of patients who did not. Results A total of 60 patients (69±12 years) were included (36 were treated with IIST and 24 were not). Patients requiring IIST were more likely to have received a combination of ICIs (39% vs 8%, p=0.01), and developed the first symptoms/signs of myocarditis earlier after the onset of ICI therapy (median, 18 days vs 60 days, p=0.002). They had a significantly higher prevalence of sustained ventricular arrhythmia, complete atrioventricular block, cardiogenic shock and troponin elevation. Moreover, they were more likely to have other immune-related adverse events simultaneously (p<0.0001), especially myositis (p=0.0002) and myasthenia gravis (p=0.009). Patients who required IIST were more likely to die from any cause (50% vs 21%, p=0.02). Among them, patients who received infliximab were more likely to die from cardiovascular causes (OR, 12.0; 95% CI 2.1 to 67.1; p=0.005). Conclusion The need for IIST was more common in patients who developed myocarditis very early after the start of ICI therapy, as well as when hemodynamic/electrical instability or neuromuscular adverse events occurred. Treatment with infliximab might be associated with an increased risk of cardiovascular death.
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Affiliation(s)
- Jennifer Cautela
- University Mediterranean Centre of Cardio-Oncology (MEDI-CO centre), Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, Nord Hospital, Centre for CardioVascular and Nutrition research (C2VN), INSERM 1263, INRAE 1260, Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille, Marseille, Provence-Alpes-Côte d'Azur, France.,Mediterranean Group of Cardio-oncology (gMEDICO), Aix-Marseille-University, Marseille, Provence-Alpes-Côte d'Azur, France
| | - Sarah Zeriouh
- University Mediterranean Centre of Cardio-Oncology (MEDI-CO centre), Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, Nord Hospital, Centre for CardioVascular and Nutrition research (C2VN), INSERM 1263, INRAE 1260, Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille, Marseille, Provence-Alpes-Côte d'Azur, France
| | - Melanie Gaubert
- University Mediterranean Centre of Cardio-Oncology (MEDI-CO centre), Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, Nord Hospital, Centre for CardioVascular and Nutrition research (C2VN), INSERM 1263, INRAE 1260, Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille, Marseille, Provence-Alpes-Côte d'Azur, France
| | - Laurent Bonello
- University Mediterranean Centre of Cardio-Oncology (MEDI-CO centre), Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, Nord Hospital, Centre for CardioVascular and Nutrition research (C2VN), INSERM 1263, INRAE 1260, Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille, Marseille, Provence-Alpes-Côte d'Azur, France
| | - Marc Laine
- University Mediterranean Centre of Cardio-Oncology (MEDI-CO centre), Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, Nord Hospital, Centre for CardioVascular and Nutrition research (C2VN), INSERM 1263, INRAE 1260, Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille, Marseille, Provence-Alpes-Côte d'Azur, France
| | - Michael Peyrol
- University Mediterranean Centre of Cardio-Oncology (MEDI-CO centre), Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, Nord Hospital, Centre for CardioVascular and Nutrition research (C2VN), INSERM 1263, INRAE 1260, Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille, Marseille, Provence-Alpes-Côte d'Azur, France
| | - Franck Paganelli
- University Mediterranean Centre of Cardio-Oncology (MEDI-CO centre), Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, Nord Hospital, Centre for CardioVascular and Nutrition research (C2VN), INSERM 1263, INRAE 1260, Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille, Marseille, Provence-Alpes-Côte d'Azur, France
| | - Nathalie Lalevee
- University Mediterranean Centre of Cardio-Oncology (MEDI-CO centre), Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, Nord Hospital, Centre for CardioVascular and Nutrition research (C2VN), INSERM 1263, INRAE 1260, Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille, Marseille, Provence-Alpes-Côte d'Azur, France.,Technological Advances for Genomics and Clinics (TAGC), UMR/INSERM 1090, Aix-Marseille-University, Marseille, France
| | - Fabrice Barlesi
- Mediterranean Group of Cardio-oncology (gMEDICO), Aix-Marseille-University, Marseille, Provence-Alpes-Côte d'Azur, France.,Gustave Roussy, Drug Development Department (DITEP), Paris-Saclay University, Villejuif, France
| | - Franck Thuny
- University Mediterranean Centre of Cardio-Oncology (MEDI-CO centre), Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, Nord Hospital, Centre for CardioVascular and Nutrition research (C2VN), INSERM 1263, INRAE 1260, Aix-Marseille University, Assistance Publique - Hôpitaux de Marseille, Marseille, Provence-Alpes-Côte d'Azur, France .,Mediterranean Group of Cardio-oncology (gMEDICO), Aix-Marseille-University, Marseille, Provence-Alpes-Côte d'Azur, France
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Lazzerini PE, Capecchi PL, Galeazzi M, Laghi-Pasini F. Biologic drugs and arrhythmic risk in chronic inflammatory arthritis: the good and the bad. Immunol Res 2018; 65:262-275. [PMID: 27423435 DOI: 10.1007/s12026-016-8833-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Increasing evidence indicates that patients with chronic inflammatory arthritis (CIA), including rheumatoid arthritis and spondyloarthropathies, have an increased risk of arrhythmic events, significantly contributing to the higher cardiovascular disease (CVD) morbidity and mortality observed in these subjects compared to the general population. Although the mechanisms accounting for such an arrhythmogenic substrate are not fully understood, the main role is probably played by chronic systemic inflammation, able to accelerate the development of structural CVD, as well as to directly affect cardiac electrophysiology. In the past decade, biologic therapies have revolutionized the treatment of CIA by highly enhancing the probability to effectively control disease activity and its systemic consequences, including cardiovascular involvement. Accordingly, accumulating data demonstrated that by potently inhibiting systemic inflammation, biologic drugs can reduce CVD progression and ameliorate arrhythmic risk parameters, with a putative beneficial impact on arrhythmia incidence. Nevertheless, a significant number of reports from clinical trials and postmarketing experience suggest that some of these medications, particularly TNF inhibitor monoclonal antibodies and rituximab, may in some circumstances precipitate arrhythmia occurrence, probably by acutely amplifying myocardial electric instability intrinsically associated with these diseases. In this review, we analyze the intricate link between biologic drugs and arrhythmias in CIA in the effort to identify which factors are involved in the fine-tuning of antiarrhythmic/pro-arrhythmic balance, and understand how this knowledge should be translated in the clinical practice to obtain the most favorable benefit-to-risk profile when biologic drugs are used in these patients.
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Affiliation(s)
- Pietro Enea Lazzerini
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Policlinico "Le Scotte", Viale Bracci, Siena, Italy.
| | - Pier Leopoldo Capecchi
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Policlinico "Le Scotte", Viale Bracci, Siena, Italy
| | - Mauro Galeazzi
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Policlinico "Le Scotte", Viale Bracci, Siena, Italy
| | - Franco Laghi-Pasini
- Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Policlinico "Le Scotte", Viale Bracci, Siena, Italy
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Masoud S, Lim PB, Kitas GD, Panoulas V. Sudden cardiac death in patients with rheumatoid arthritis. World J Cardiol 2017; 9:562-573. [PMID: 28824786 PMCID: PMC5545140 DOI: 10.4330/wjc.v9.i7.562] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2016] [Revised: 03/15/2017] [Accepted: 04/19/2017] [Indexed: 02/06/2023] Open
Abstract
An increased cardiovascular morbidity and mortality, including the risk of sudden cardiac death (SCD), has been shown in patients with rheumatoid arthritis (RA). Abnormalities in autonomic markers such as heart rate variability and ventricular repolarization parameters, such as QTc interval and QT dispersion, have been associated with sudden death in patients with RA. The interplay between these parameters and inflammation that is known to exist with RA is of growing interest. In this article, we review the prevalence and predictors of SCD in patients with RA and describe the potential underlying mechanisms, which may contribute to this. We also review the impact of biologic agents on arrhythmic risk as well as cardiovascular morbidity and mortality.
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10
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Lankarani KB. Letter: rapid infliximab infusion is not always safe. Aliment Pharmacol Ther 2013; 38:844. [PMID: 24001101 DOI: 10.1111/apt.12447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2013] [Accepted: 07/19/2013] [Indexed: 02/05/2023]
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Side effects of TNF-α blockers in patients with psoriatic arthritis: evidences from literature studies. Clin Rheumatol 2013; 32:743-53. [PMID: 23588881 DOI: 10.1007/s10067-013-2252-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2013] [Revised: 03/20/2013] [Accepted: 03/27/2013] [Indexed: 12/13/2022]
Abstract
Psoriatic arthritis is an inflammatory rheumatic disorder, which occurs in patients with skin and/or nail psoriasis. In psoriatic arthritis, the importance of biologic mediators modulating inflammatory reaction, such as tumor necrosis factor, and the knowledge on their role in the pathogenesis of psoriatic arthritis influence the therapeutic choices. In the last years, the introduction of biologic drugs has greatly changed the treatment of psoriasis and psoriatic arthritis. In fact, tumor necrosis factor-α blockers demonstrated an effective action in the treatment of both skin and joint manifestations of psoriatic arthritis, but they have some adverse effects. The aim of this review is to revisit the literature data on adverse effects of tumor necrosis factor-α blockers in patients with psoriatic arthritis.
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Mousa SA, Goncharuk O, Miller D. Recent advances of TNF-α antagonists in rheumatoid arthritis and chronic heart failure. Expert Opin Biol Ther 2007; 7:617-25. [PMID: 17477800 DOI: 10.1517/14712598.7.5.617] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Tumor necrosis factor (TNF)-alpha has been thoroughly investigated and established as a pivotal component of the inflammatory cascade. This review encompasses the safety and efficacy of TNF antagonists in rheumatoid arthritis, the interplay between rheumatoid arthritis and heart failure, as well as presentation of the available preclinical and clinical data discussing the use of anti-TNF therapy in patients with chronic heart failure. There is well-documented evidence for the role of anti-TNF-alpha in rheumatoid arthritis, in contrast to the controversial role of anti-TNF-alpha in heart failure. In animal models and small-scale clinical trials, anti-TNF therapy showed some promise in treating chronic heart failure, whereas larger, multicenter, randomized, placebo-controlled clinical trials (i.e., RECOVER [Research into Etanercept Cytokine Antagonism in Ventricular Dysfunction] and RENAISSANCE [Randomized Etanercept North American Strategy to Study Antagonism of Cytokines]) failed to show a statistically significant difference in composite clinical function score for anti-TNF therapy versus placebo. Future investigation is needed to determine if individualized dosing of anti-TNF therapy is necessary and whether or not treating patients with earlier-stage disease will show a benefit.
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Affiliation(s)
- Shaker A Mousa
- Pharmaceutical Research Institute at Albany, Albany College of Pharmacy, 106 New Scotland Avenue, Albany, NY 12208, USA.
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Barbato M, Curione M, Viola F, Versacci P, Parisi F, Amato S, Cucchiara S. Cardiac involvement in children with IBD during infliximab therapy. Inflamm Bowel Dis 2006; 12:828-9. [PMID: 16917240 DOI: 10.1097/00054725-200608000-00021] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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Gamarra RM, McGraw SD, Drelichman VS, Maas LC. Serum sickness-like reactions in patients receiving intravenous infliximab. J Emerg Med 2006; 30:41-4. [PMID: 16434333 DOI: 10.1016/j.jemermed.2005.01.033] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2003] [Revised: 12/01/2004] [Accepted: 01/26/2005] [Indexed: 01/06/2023]
Abstract
Infliximab, a monoclonal antibody against tumor necrosis factor (TNF) has been used successfully for the treatment of certain forms of Crohn's disease and rheumatoid arthritis. Both acute and delayed hypersensitivity reactions have been associated with the intravenous use of this drug. The delayed forms may present as a serum sickness-like illness and recognition of the clinical manifestations becomes crucial for early diagnosis and treatment. With the dramatic increase in the use of infliximab, there will likely be increased numbers of patients with this type of reaction. These patients may have received this drug days or even weeks before the clinical presentation. These types of reactions also have been reported with the use of other monoclonal antibodies.
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Affiliation(s)
- Roberto M Gamarra
- Department of Internal Medicine, Providence Hospital, Southfield, Michigan 48075, USA
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del Rincón I, Escalante A. Update of tnf-alpha antagonists and cardiovascular disease in rheumatoid arthritis. Curr Rheumatol Rep 2005; 7:395-9. [PMID: 16174491 DOI: 10.1007/s11926-005-0028-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Tumor necrosis factor-alpha (TNF-alpha) antagonists were unexpectedly found to have no beneficial effects in moderate-to-severe heart failure in two large randomized clinical trials. In certain doses, the agents were found to be harmful. These results have important implications for rheumatoid arthritis (RA). Patients with the disease have an increased risk for developing cardiovascular co-morbidity, including heart failure. Because of the beneficial effect of the TNF-alpha antagonists in the management of RA, these agents have gained widespread use. Rheumatologists and other physicians who provide care for RA are thus likely to encounter candidates for anti-TNF-alpha therapy who have overt or subclinical heart failure. Although data are currently not sufficient to support evidence-based recommendations, it is possible to make reasonable suggestions to guide clinical practice.
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Affiliation(s)
- Inmaculada del Rincón
- University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
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Hyrich KL, Silman AJ, Watson KD, Symmons DPM. Anti-tumour necrosis factor alpha therapy in rheumatoid arthritis: an update on safety. Ann Rheum Dis 2004; 63:1538-43. [PMID: 15242866 PMCID: PMC1754871 DOI: 10.1136/ard.2004.024737] [Citation(s) in RCA: 118] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Anti-TNFalpha therapy may have associated risks of serious infection, congestive heart failure, malignancy, and multiple sclerosis. The magnitude of these risks is difficult to assess. This article reviews publications on the current knowledge about the safety of these agents.
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Affiliation(s)
- K L Hyrich
- ARC Epidemiology Unit, University of Manchester, Oxford Road, Manchester M13 9PT, UK
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Altieri P, Brunelli C, Garibaldi S, Nicolino A, Ubaldi S, Spallarossa P, Olivotti L, Rossettin P, Barsotti A, Ghigliotti G. Metalloproteinases 2 and 9 are increased in plasma of patients with heart failure. Eur J Clin Invest 2003; 33:648-56. [PMID: 12864774 DOI: 10.1046/j.1365-2362.2003.01187.x] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Progression of heart failure is associated with interstitial changes in the heart and in areas distant from the heart. Enhanced expression of metalloproteinases 2 and 9 and of metalloproteinases tissue inhibitors 1 and 2 have been found in ventricular tissue of patients with heart failure. Our aim was to determine whether increased activity of metalloproteinase-2, metalloproteinase-9 and of metalloproteinases tissue inhibitor-1 and metalloproteinases tissue inhibitor-2 were also present in plasma of patients with heart failure. DESIGN Levels of metalloproteinase-2, metalloproteinase-9 and of metalloproteinase tissue inhibitor-1 and metalloproteinases tissue inhibitor-2 were measured in venous blood of 51 patients with heart failure, and were compared with levels of 52 control subjects. Samples collected from patients and control subjects were assayed for gelatinolytic activity (zymography) and for protein levels. RESULTS Compared with the control subjects, the patients with heart failure had a significant increase in activity levels (mean +/- SE, ng mL(-1)) of prometalloproteinase-9 (95.1+/-11.2 and 38.9+/-4.5*), activ. metalloproteinase-9 (18.4+/-2.5 and 10.9+/-1.3*), and of prometalloproteinase-2 (571.4+/-26.1 and 456.8+/-21.1*) (respectively: patients and control subjects; *P<0.05). Metalloproteinases tissue inhibitor-1, but not metalloproteinases tissue inhibitor-2 protein values were higher in the patients. Among the patients, clinical status and New York Heart Association (NYHA) class did not correlate with the metalloproteinase concentrations. Positive correlations with left ventricular volumes, and negative correlations with lipid values were obtained for prometalloproteinase-2; positive correlations with total number of white cells and neutrophils were obtained for prometalloproteinase-9; and positive correlations with lactate dehydrogenase, serum fibrinogen, aspartate transaminases were found for activ. metalloproteinase-9. CONCLUSIONS Regardless of the clinical phase of heart failure, elevated levels of activity and of circulating metalloproteinase protein levels suggest the presence of persistent extracellular remodeling in patients with heart failure.
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Affiliation(s)
- P Altieri
- Department of Internal Medicine, University of Genova, Genova, Italy
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von der Thüsen JH, Kuiper J, van Berkel TJC, Biessen EAL. Interleukins in atherosclerosis: molecular pathways and therapeutic potential. Pharmacol Rev 2003; 55:133-66. [PMID: 12615956 DOI: 10.1124/pr.55.1.5] [Citation(s) in RCA: 147] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Interleukins are considered to be key players in the chronic vascular inflammatory response that is typical of atherosclerosis. Thus, the expression of proinflammatory interleukins and their receptors has been demonstrated in atheromatous tissue, and the serum levels of several of these cytokines have been found to be positively correlated with (coronary) arterial disease and its sequelae. In vitro studies have confirmed the involvement of various interleukins in pro-atherogenic processes, such as the up-regulation of adhesion molecules on endothelial cells, the activation of macrophages, and smooth muscle cell proliferation. Furthermore, studies in mice deficient or transgenic for specific interleukins have demonstrated that, whereas some interleukins are indeed intrinsically pro-atherogenic, others may have anti-atherogenic qualities. As the roles of individual interleukins in atherosclerosis are being uncovered, novel anti-atherogenic therapies, aimed at the modulation of interleukin function, are being explored. Several approaches have produced promising results in this respect, including the transfer of anti-inflammatory interleukins and the administration of decoys and antibodies directed against proinflammatory interleukins. The chronic nature of the disease and the generally pleiotropic effects of interleukins, however, will demand high specificity of action and/or effective targeting to prevent the emergence of adverse side effects with such treatments. This may prove to be the real challenge for the development of interleukin-based anti-atherosclerotic therapies, once the mediators and their targets have been delineated.
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Affiliation(s)
- Jan H von der Thüsen
- Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden, The Netherlands.
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