Reduction Of Adverse Effects Research Articles

Allo-polyherbal Approaches for Managing Metabolic Syndrome: A Narrative Review

Abstract: Metabolic syndrome (MS) represents a complex cluster of medical conditions with profound implications for global public health. This constellation of disorders substantially increases the susceptibility to type 2 diabetes, obesity, thrombosis, cardiovascular disease, and hyperlipidemia. The drugs currently prescribed for managing MS offer limited efficacy, likely due to their limited scope of action. Owing to their restricted mechanisms of action, these medications often lead to significant side effects such as weight gain, bone marrow impairment, Raynaud's phenomenon, galactorrhea, and others. Consequently, these adverse effects contribute to poor patient adherence and restrict the overall effectiveness of the treatment. Thus, developing new therapeutic strategies for managing MS is certainly required. Recent investigations have been concentrated on formulating strategies that combine conventional synthetic drugs with herbal medicines (which act via multiple targets), aiming to enhance treatment efficacy and enhance patient adherence in the management of MS. This concept of combining synthetic and herbal drugs is termed ‘Allo-polyherbal’ and has been shown to improve the efficacy of synthetic drugs and reduction of adverse effects. The present review uncovers the concept of Allo-polyherbal and reveals the potential benefits of using Allopolyherbal in managing diabetes, cardiovascular, hypertension, hyperlipidemia, obesity, and thrombosis leading to MS.

P755 Long-term need for restart of biologics after withdrawal in patients with Inflammatory Bowel Disease in mucosal healing

Abstract Background In patients with inflammatory bowel disease (IBD) on biologic therapy, once remission has been achieved, withdrawal is a frequent issue in clinical practice that generates uncertainty in aspects such as the reduction of adverse effects and costs, but also the risk of recurrence of activity and the need to restart treatment. The aim of this study was to determine the rate of long-term reintroduction of biologics after withdrawal due to mucosal healing (MH) in IBD, the response to reintroduction and the associated factors. Methods Observational, descriptive, single-centre, retrospective, descriptive study of 178 cases in 164 patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) who were withdrawn from anti-tumor necrosis factor (anti- TNF) therapy once MH had been demonstrated, between July 2009 and February 2022. Demographic and phenotypic characteristics of IBD, characteristics of biologic and immunosuppressive therapy, analytical and endoscopic/histological variables at the time of withdrawal were collected. We analysed the risk of restarting biologics due to clinical relapse and response to reintroduction of treatment. We evaluated possible factors related to the risk of restarting treatment and response to treatment. Results We included 178 cases. 123 CD and 55 UC. Most had received infliximab (62.9%) and the main indication was corticodependence (68%). Median follow-up was 78 months (IQR 59-95). Clinical relapse occurred in 69% of cases and 61.2% required reintroduction of biologics, with the probability of retreatment at 1, 3, 5 and 7 years being 19.4%, 50%, 60% and 63.4%, respectively (Figure 1). The response to reintroduction was 86.2%. Only 1.68% required surgery during follow-up. Univariate analysis showed higher risk of re-introduction at younger age at diagnosis (23 vs 30 vs 30, p 0.022) and at withdrawal (32 vs 40, p 0.019) and longer follow-up time after withdrawal (82 vs 71, p 0.026). Multivariate analysis also identified the indication for corticodependence (p 0.046). Conclusion The risk of relapse and re-starting treatment is high in the long term after withdrawal of biologic therapy for MH in IBD. Younger age at diagnosis and withdrawal, indication for corticodependence and long-term follow-up are risk factors for poor outcome. Reintroduction of treatment is very effective with low complication rates.

Lebrikizumab: a novel approach in managing atopic dermatitis in pediatric patients

Atopic dermatitis is a prominent dermatological condition in children that frequently affects their lifestyle. Conventional treatments frequently prove inadequate, necessitating the use of biological agents like Lebrikizumab to address the condition at its core pathophysiological level. The introduction of biologic drugs has broadened the spectrum of treatment options for patients with moderate to severe atopic dermatitis, especially those who have not achieved satisfactory results with conventional monotherapy or combination therapies, or those with contraindications to systemic immunosuppressive agents. Lebrikizumab appears to be a promising option for the treatment of atopic dermatitis, showing a strong response in clinical trials. It offers the potential for improved long-term efficacy and a reduction in adverse effects. This article provides an overview of Lebrikizumab's role in addressing the pathogenesis of atopic dermatitis and highlights its current advancements.

Development and Functionalization of a Novel Chitosan-Based Nanosystem for Enhanced Drug Delivery.

Nowadays, infection diseases are one of the most significant threats to humans all around the world. An encouraging strategy for solving this issue and fighting resistant microorganisms is to develop drug carriers for a prolonged release of the antibiotic to the target site. The purpose of this work was to obtain metronidazole-encapsulated chitosan nanoparticles using an ion gelation route and to evaluate their properties. Due to the advantages of the ionic gelation method, the synthesized polymeric nanoparticles can be applied in various fields, especially pharmaceutical and medical. Loading capacity and encapsulation efficiency varFied depending on the amount of antibiotic in each formulation. Physicochemical characterization using scanning electron microscopy revealed a narrow particle size distribution where 90% of chitosan particles were 163.7 nm in size and chitosan-loaded metronidazole nanoparticles were 201.3 nm in size, with a zeta potential value of 36.5 mV. IR spectra revealed characteristic peaks of the drug and polymer nanoparticles. Cell viability assessment revealed that samples have no significant impact on tested cells. Release analysis showed that metronidazole was released from the chitosan matrix for 24 h in a prolonged course, implying that antibiotic-encapsulated polymer nanostructures are a promising drug delivery system to prevent or to treat various diseases. It is desirable to obtain new formulations based on drugs encapsulated in nanoparticles through different preparation methods, with reduced cytotoxic potential, in order to improve the therapeutic effect through sustained and prolonged release mechanisms of the drug correlated with the reduction of adverse effects.

Artículo traducido] Caracterización y resultados del uso de voriconazol nebulizado en un entorno real: un estudio observacional unicéntrico

ObjectivePulmonary administration of voriconazole involves advantages, including optimization of lung penetration and reduction of adverse effects and interactions. However, there is scarce evidence about its use and there are no commercial presentations for nebulization. We aim to characterize a compounded voriconazole solution for nebulization and describe its use in our center. MethodThis is a retrospective observational study including patients who received nebulized voriconazole to treat fungal lung diseases (infection or colonization). Voriconazole solution was prepared from commercial vials for intravenous administration. ResultsThe pH and osmolarity of voriconazole solutions were adequate for nebulization. Ten patients were included, nine adults and a child. The dosage was 40 mg in adults and 10 mg in the pediatric patient, diluted to a final concentration of 10 mg/ml, administered every 12-24 hours. The median duration of treatment was 139 (range: 26-911) days. There were no reported adverse effects and the drug was not detected in plasma when nebulized only. ConclusionVoriconazole nebulization is well tolerated and it is not absorbed into the systemic circulation; further research is needed to assess its efficacy.

RATIONAL MANAGEMENT OF INSECTICIDES IN MONOCULTURE AREAS

In Mexico, some monocultures occupy large areas, and organo-synthetic insecticides are the dominant method of pest control. The conventional chemical strategy is heavily reliant on new insecticides being developed in other countries. This paper discusses the characteristics of traditional/conventional and rational insecticide management. In traditional management, companies compete to position their products in the market once authorized. When pests develop resistance, the farmer must increase the dose and frequency of applications. These actions seriously threaten the environment, human health, and crop profitability. The hope is that another insecticide will enter the market to repeat the cycle of abuse and its consequences. The alternative is a rational strategy based on scientific evidence for chemical pest control. Farmers must adhere to an insecticide resistance management program that keeps resistance gene expression and intensity at acceptable levels. We propose the creation of public and private laboratories to systematically estimate the dynamics of insecticide resistance through bioassays. This will enable decisions to be made based on scientific rather than commercial information. Changing the current paradigm for the use of these agrochemicals will result in significant improvements in the time it takes to maintain acceptable biological efficacy, economic benefits to the producer, and significant reductions in adverse effects on human health and the environment.

Characterization and real-live results of nebulized voriconazole: A single-center observational study

ObjectivePulmonary administration of voriconazole involves advantages, including optimization of lung penetration and reduction of adverse effects and interactions. However, there is scarce evidence about its use and there are no commercial presentations for nebulization. We aim to characterize a compounded voriconazole solution for nebulization and describe its use in our center. MethodThis is a retrospective observational study including patients who received nebulized voriconazole to treat fungal lung diseases (infection or colonization). Voriconazole solution was prepared from commercial vials for intravenous administration. ResultsThe pH and osmolarity of voriconazole solutions were adequate for nebulization. Ten patients were included, 9 adults and a child. The dosage was 40 mg in adults and 10 mg in the pediatric patient, diluted to a final concentration of 10 mg/ml, administered every 12–24 h. The median duration of treatment was 139 (range: 26–911) days. There were no reported adverse effects and the drug was not detected in plasma when nebulized only. ConclusionVoriconazole nebulization is well-tolerated and it is not absorbed into the systemic circulation; further research is needed to assess its efficacy.

Expert Review and Consensus on the Treat-to-Target Management of Hereditary Angioedema: From Scientific Evidence to Clinical Practice.

Hereditary angioedema with C1 inhibitor deficiency (HAE-C1INH) is a rare disease characterized by swelling episodes. It affects quality of life (QOL) and can be fatal when the upper airways are involved. Treatment is individualized, with therapeutic options including on-demand treatment (ODT) and short- and long-term prophylaxis (STP, LTP). However, available guidelines are not always clear about the selection of treatment, the goals of treatment, or how achievement of these goals is assessed. To review available evidence for the management of HAE-C1INH and build a Spanish expert consensus to steer management towards a treat-to-target approach, while addressing some of the less clear aspects of the Spanish guidelines. We reviewed the literature on the treat-to-target management of HAE-C1INH, focusing on treatment selection and goals and the tools available to assess whether the goals have been achieved. We discussed the literature based on clinical experience and drew up 45 statements on undefined management aspects. A panel of 53 HAE experts validated the statements through a 2-round Delphi process. The goals for ODT and STP are to minimize the morbidity and mortality of attacks and to prevent attacks caused by known triggers, respectively, while the main goal of LTP is to decrease the rate, severity, and duration of attacks. Furthermore, when prescribing, clinicians should consider the reduction in adverse effects, while increasing patient QOL and satisfaction. Appropriate instruments for assessing achievement of treatment goals are also indicated. We provide recommendations on previously unclear aspects of HAE-C1INH management with ODT, STP, and LTP, focusing on clinical and patient-oriented goals.

Low-dose naltrexone for treatment of pain in patients with fibromyalgia: a randomized, double-blind, placebo-controlled, crossover study.

Fibromyalgia (FM) is a chronic fluctuating, nociplastic pain condition. Naltrexone is a µ-opioid-receptor antagonist; preliminary studies have indicated a pain-relieving effect of low-dose naltrexone (LDN) in patients with FM. The impetus for studying LDN is the assumption of analgesic efficacy and thus reduction of adverse effects seen from conventional pharmacotherapy. First, to examine if LDN is associated with analgesic efficacy compared with control in the treatment of patients with FM. Second, to ascertain the analgesic efficacy of LDN in an experimental pain model in patients with FM evaluating the competence of the descending inhibitory pathways compared with controls. Third, to examine the pharmacokinetics of LDN. The study used a randomized, double-blind, placebo-controlled, crossover design and had a 3-phase setup. The first phase included baseline assessment and a treatment period (days -3 to 21), the second phase a washout period (days 22-32), and the third phase a baseline assessment followed by a treatment period (days 33-56). Treatment was with either LDN 4.5 mg or an inactive placebo given orally once daily. The primary outcomes were Fibromyalgia Impact Questionnaire revised (FIQR) scores and summed pain intensity ratings (SPIR). Fifty-eight patients with FM were randomized. The median difference (IQR) for FIQR scores between LDN and placebo treatment was -1.65 (18.55; effect size = 0.15; P = 0.3). The median difference for SPIR scores was -0.33 (6.33; effect size = 0.13; P = 0.4). Outcome data did not indicate any clinically relevant analgesic efficacy of the LDN treatment in patients with FM.

Sphingomyelin-Rich Lipid Extract Collar for Canine Atopic Dermatitis.

The management of canine atopic dermatitis (CAD) is complex, and it needs to be multimodal, combining topical and systemic therapies. Given that the currently available options are not always totally effective and might have some associated adverse effects, novel alternatives are needed. For this reason, a new collar for CAD was developed with 2.5% of a sphingomyelin-rich lipid extract (LE) with proven benefits for skin health. The release of the active ingredient when incorporated into the collar was tested in vitro, showing an adequate kinetic profile. Then, the efficacy and safety of the collar were assessed in 12 client-owned dogs with CAD in a pilot study. After eight weeks, the dogs experienced significant clinical improvements on the Canine Atopic Dermatitis Extent and Severity Index (CADESI)-4, Pruritus Index for Canine Atopic Dermatitis (PCAD) and Pruritus Visual Analogue Scale (PVAS) scores, without any adverse effects. Additionally, further in vitro studies were performed, indicating that this LE collar should be compatible with antiparasitic collars (with deltamethrin or imidacloprid/flumethrin) if worn simultaneously. Given the observed benefits of this LE collar, combining it with other CAD therapies could potentially allow for drug sparing, reduction in adverse effects, enhanced owner compliance, and reduced treatment costs.

Controlled Release and Cell Viability of Ketoconazole Incorporated in PEG 4000 Derivatives.

In recent years, polymeric materials have been gaining prominence in studies of controlled release systems to obtain improvements in drug administration. These systems present several advantages compared with conventional release systems, such as constant maintenance in the blood concentration of a given drug, greater bioavailability, reduction of adverse effects, and fewer dosages required, thus providing a higher patient compliance to treatment. Given the above, the present work aimed to synthesize polymeric matrices derived from polyethylene glycol (PEG) capable of promoting the controlled release of the drug ketoconazole in order to minimize its adverse effects. PEG 4000 is a widely used polymer due to its excellent properties such as hydrophilicity, biocompatibility, and non-toxic effects. In this work, PEG 4000 and derivatives were incorporated with ketoconazole. The morphology of polymeric films was observed by AFM and showed changes on the film organization after drug incorporation. In SEM, it was possible to notice spheres that formed in some incorporated polymers. The zeta potential of PEG 4000 and its derivatives was determined and suggested that the microparticle surfaces showed a low electrostatic charge. Regarding the controlled release, all the incorporated polymers obtained a controlled release profile at pH 7.3. The release kinetics of ketoconazole in the samples of PEG 4000 and its derivatives followed first order for PEG 4000 HYDR INCORP and Higuchi for the other samples. Cytotoxicity was determined and PEG 4000 and its derivatives were not cytotoxic.

Reconsidering the route of drug delivery in refractory multiple sclerosis: Toward a more effective drug accumulation in the central nervous system.

Multiple sclerosis is a chronic demyelinating disease with different disease phenotypes. The current FDA-approved disease-modifying therapeutics (DMTs) cannot cure the disease, but only alleviate the disease progression. While the majority of patients respond well to treatment, some of them are suffering from rapid progression. Current drug delivery strategies include the oral, intravenous, subdermal, and intramuscular routes, so these drugs are delivered systemically, which is appropriate when the therapeutic targets are peripheral. However, the potential benefits may be diminished when these targets sequester behind the barriers of the central nervous system. Moreover, systemic drug administration is plagued with adverse effects, sometimes severe. In this context, it is prudent to consider other drug delivery strategies improving their accumulation in the brain, thus providing better prospects for patients with rapidly progressing disease course. These targeted drug delivery strategies may also reduce the severity of systemic adverse effects. Here, we discuss the possibilities and indications for reconsideration of drug delivery routes (especially for those "non-responding" patients) and the search for alternative drug delivery strategies. More targeted drug delivery strategies sometimes require quite invasive procedures, but the potential therapeutic benefits and reduction of adverse effects could outweigh the risks. We characterized the major FDA-approved DMTs focusing on their therapeutic mechanism and the potential benefits of improving the accumulation of these drugs in the brain.

Respiratory Monitoring During Mechanical Ventilation: The Present and the Future.

The increased application of mechanical ventilation, the recognition of its harms and the interest in individualization raised the need for an effective monitoring. An increasing number of monitoring tools and modalities were introduced over the past 2 decades with growing insight into asynchrony, lung and chest wall mechanics, respiratory effort and drive. They should be used in a complementary rather than a standalone way. A sound strategy can guide a reduction in adverse effects like ventilator-induced lung injury, ventilator-induced diaphragm dysfunction, patient-ventilator asynchrony and helps early weaning from the ventilator. However, the diversity, complexity, lack of expertise, and associated cost make formulating the appropriate monitoring strategy a challenge for clinicians. Most often, a big amount of data is fed to the clinicians making interpretation difficult. Therefore, it is fundamental for intensivists to be aware of the principle, advantages, and limits of each tool. This analytic review includes a simplified narrative of the commonly used basic and advanced respiratory monitors along with their limits and future prospective.

Stewardship applied to antipsychotics: Development of an antipsychotic stewardship program in inpatient settings for monitoring and optimizing outcomes.

Antipsychotic (AP) medications are prescribed for various psychiatric diagnoses that require routine monitoring to ensure optimal use, effectiveness, adherence, and for potentially severe adverse effects. There is currently no comprehensive protocol for institutional supervision of prescribing and monitoring AP. Antibiotics (ABX) are commonly associated with stewardship programs aimed at optimizing use and mitigating harm. These programs have proven to result in positive outcomes in both safety and efficacy parameters for numerous institutions. Given that AP are also associated with significant adverse effects and often misused, the concept of stewardship can be applied to this class of agents to optimize their use and improve overall patient outcomes. The objective of this paper is to provide guidance for the implementation of antipsychotic stewardship programs (APSP) in the inpatient setting. The development of this APSP was designed based on ABX stewardship programs and the Centers for Disease Control and Prevention, Agency for Healthcare Research and Quality, and the American Psychiatric Association practice guidelines on the treatment of patients with schizophrenia. In conclusion, APSPs have the potential to enhance and standardize institutional supervision of prescribing and monitoring practices of AP, leading to improved clinical outcomes and the reduction of adverse effects. APSP teams should be multidisciplinary, consisting of clinicians and administrators, working in conjunction with patients and patient advocates to design individualized recovery plans that consider the individual patient's history and desired outcomes. Monitoring, stewardship interventions, and outcomes should be documented on both an individual and deidentified institutional basis, analyzed, and summarized periodically as measures for quality improvement.

Inhaled aviptadil for the possible treatment of COVID-19 in patients at high risk for ARDS: study protocol for a randomized, placebo-controlled, and multicenter trial

BackgroundDespite the fast establishment of new therapeutic agents in the management of COVID-19 and large-scale vaccination campaigns since the beginning of the SARS-CoV-2 pandemic in early 2020, severe disease courses still represent a threat, especially to patients with risk factors. This indicates the need for alternative strategies to prevent respiratory complications like acute respiratory distress syndrome (ARDS) associated with COVID-19. Aviptadil, a synthetic form of human vasoactive intestinal peptide, might be beneficial for COVID-19 patients at high risk of developing ARDS because of its ability to influence the regulation of exaggerated pro-inflammatory proteins and orchestrate the lung homeostasis. Aviptadil has recently been shown to considerably improve the prognosis of ARDS in COVID-19 when applied intravenously. An inhaled application of aviptadil has the advantages of achieving a higher concentration in the lung tissue, fast onset of activity, avoiding the hepatic first-pass metabolism, and the reduction of adverse effects. The overall objective of this project is to assess the efficacy and safety of inhaled aviptadil in patients hospitalized for COVID-19 at high risk of developing ARDS.MethodsThis multicenter, placebo-controlled, double-blinded, randomized trial with 132 adult patients hospitalized for COVID-19 and at high risk for ARDS (adapted early acute lung injury score ≥ 2 points) is conducted in five public hospitals in Europe. Key exclusion criteria are mechanical ventilation at baseline, need for intensive care at baseline, and severe hemodynamic instability. Patients are randomly allocated to either inhale 67 μg aviptadil or normal saline (three times a day for 10 days), in addition to standard care, stratified by center. The primary endpoint is time from hospitalization to clinical improvement, defined as either hospital discharge, or improvement of at least two levels on the nine-level scale for clinical status suggested by the World Health Organization.DiscussionTreatment strategies for COVID-19 are still limited. In the context of upcoming new variants of SARS-CoV-2 and possible inefficacy of the available vaccines and antibody therapies, the investigation of alternative therapy options plays a crucial role in decreasing associated mortality and improving prognosis. Due to its unique immunomodulating properties also targeting the SARS-CoV-2 pathways, inhaled aviptadil may have the potential to prevent ARDS in COVID-19.Trial registrationClinicalTrials.gov, NCT04536350. Registered 02 September 2020.

Perspectives of topical formulations for melasma.

Melasma is acquired hyperpigmentation that mainly affects the face, can cause negative changes in self-esteem, and mostly affects women. Treatment is difficult, and different drugs can be used in mono or combination therapy. In this article, we present a brief overview of melasma, how to evaluate it, and a synthesis of the most commonly used topical therapies and their indications, including sunscreens, pharmacological agents, and plant extracts. Hydroquinone (4%) in monotherapy or combined with corticosteroids (dexamethasone and fluocinolone acetonide) and retinoids (tretinoin); arbutin (1%); methimazole (5%); kojic (2%), azelaic (20%), and tranexamic (5%) acids are the pharmacological agents that stand out. Correct application of these substances determines a variable improvement in melasma but often causes adverse reactions such as erythema, itching, and burning at the application site. Vitamin C can contribute to the reduction of melasma and have little or no adverse effects while sunscreens are normally used as coadjuvant therapies. In conclusion, we have compiled specific topical therapies for treating melasma and discussed those that are the most used currently. We consider it important that prescribers and researchers evaluate the best cost-benefit ratio of topical therapeutic options and develop new formulations, enabling efficacy in the treatment with safety and comfort during application, through the reduction of adverse effects.

Toxicology in the emergency department: what's new?

Intentional and accidental drug overdose, recreational drug use and exposure to toxic substances are common reasons for people presenting to emergency departments. Although the mortality rate associated with these presentations is low in the UK, they can lead to significant morbidity and prolonged hospital admissions. This review discusses new developments in the management of paracetamol overdose. Several new protocols for the infusion of acetylcysteine, the antidote for paracetamol overdose, have been proposed in the past decade and evaluated in clinical studies. The 12-hour Scottish and Newcastle Acetylcysteine Protocol regimen and 20-hour Australian two-infusion bag protocol have been widely adopted into clinical practice and endorsed in national guidelines because of their shorter duration, reduction in adverse effects and efficacy in treating overdose. This article includes a care pathway that can facilitate the implementation of the Scottish and Newcastle Acetylcysteine Protocol. This article also discusses the emergency management of ingested button batteries, describes the emerging threat of novel psychoactive substances, and provides an update on new UK antidote guidelines. Further up-to-date guidance on management of clinical toxicology is available to healthcare professionals on the internet database TOXBASE.

Micro/Nanosystems for Magnetic Targeted Delivery of Bioagents.

Targeted delivery of pharmaceuticals is promising for efficient disease treatment and reduction in adverse effects. Nano or microstructured magnetic materials with strong magnetic momentum can be noninvasively controlled via magnetic forces within living beings. These magnetic carriers open perspectives in controlling the delivery of different types of bioagents in humans, including small molecules, nucleic acids, and cells. In the present review, we describe different types of magnetic carriers that can serve as drug delivery platforms, and we show different ways to apply them to magnetic targeted delivery of bioagents. We discuss the magnetic guidance of nano/microsystems or labeled cells upon injection into the systemic circulation or in the tissue; we then highlight emergent applications in tissue engineering, and finally, we show how magnetic targeting can integrate with imaging technologies that serve to assist drug delivery.

Controlling Antimicrobial Activity of Quinolones Using Visible/NIR Light-Activated BODIPY Photocages

Controlling the activity of a pharmaceutical agent using light offers improved selectivity, reduction of adverse effects, and decreased environmental build-up. These benefits are especially attractive for antibiotics. Herein, we report a series of photoreleasable quinolones, which can be activated using visible/NIR light (520–800 nm). We have used BODIPY photocages with strong absorption in the visible to protect two different quinolone-based compounds and deactivate their antimicrobial properties. This activity could be recovered upon green or red light irradiation. A comprehensive computational study provides new insight into the reaction mechanism, revealing the relevance of considering explicit solvent molecules. The triplet excited state is populated and the photodissociation is assisted by the solvent. The light-controlled activity of these compounds has been assessed on a quinolone-susceptible E. coli strain. Up to a 32-fold change in the antimicrobial activity was measured.

De-Escalation of Anti-Tumor Necrosis Factor Alpha Agents and Reduction in Adverse Effects: A Systematic Review.

Background: The long-term use of anti-TNF-α agents can lead to adverse effects, such as infections and immune-mediated cutaneous reactions. Whether de-escalation by dose reduction or interval lengthening reduces these adverse effects is uncertain. This systematic review aims to compare the incidence of infections and skin manifestations after anti-TNF-α dose de-escalation with standard dosing. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception to 14 January 2022. Randomized controlled trials (RCTs) and observational studies comparing anti-TNF-α de-escalation strategies with standard dosing among patients with inflammatory conditions, that report on infections, skin manifestations, or both, were included. The risk of bias was assessed with the revised Cochrane risk-of bias tool (RCTs) or the Newcastle–Ottawa scale (non-RCTs). Results: Fourteen RCTs and six observational studies (or 2706 patients) were included. Eight RCTs had low risk of bias or some concerns. Four non-RCTs were of good methodological quality. The studies described patients with axial spondyloarthritis (8 studies, 780 patients), rheumatoid arthritis (7 studies, 1458 patients), psoriasis (3 studies, 332 patients), or inflammatory bowel disease (2 studies, 136 patients). De-escalation strategies included interval lengthening (12 studies, 1317 patients), dose reduction (6 studies, 1130 patients), or both (2 studies, 259 patients). Overall, the occurrence of infections and skin manifestations did not differ between standard treatment and de-escalation. The disappearance of infections or skin manifestations after de-escalation was only reported in two studies. The majority of studies focused on etanercept and adalimumab. Heterogeneity in reporting of infections and skin manifestations precluded meta-analysis. Conclusion: We found that anti-TNF-α de-escalation does not reduce infections or skin reactions. A de-escalation strategy should not be recommended for the sole purpose of reducing drug-related adverse effects. The meticulous documentation of adverse effects is recommended to further address this question. Registration: PROSPERO CRD42021252977.