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The Cochrane Database of Systematic... Jan 2020Ageing has a degenerative effect on the skin, leaving it more vulnerable to damage. Hygiene and emollient interventions may help maintain skin integrity in older people... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ageing has a degenerative effect on the skin, leaving it more vulnerable to damage. Hygiene and emollient interventions may help maintain skin integrity in older people in hospital and residential care settings; however, at present, most care is based on "tried and tested" practice, rather than on evidence.
OBJECTIVES
To assess the effects of hygiene and emollient interventions for maintaining skin integrity in older people in hospital and residential care settings.
SEARCH METHODS
We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL, up to January 2019. We also searched five trials registers.
SELECTION CRITERIA
Randomised controlled trials comparing hygiene and emollient interventions versus placebo, no intervention, or standard practices for older people aged ≥ 60 years in hospital or residential care settings.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by Cochrane. Primary outcomes were frequency of skin damage, for example, complete loss of integrity (tears or ulceration) or partial loss of integrity (fissuring), and side effects. Secondary outcomes included transepidermal water loss (TEWL), stratum corneum hydration (SCH), erythema, and clinical scores of dryness or itch. We used GRADE to assess the quality of evidence.
MAIN RESULTS
We included six trials involving 1598 residential care home residents; no included trial had a hospital setting. Most participants had a mean age of 80+ years; when specified, more women were recruited than men. Two studies included only people with diagnosed dry skin. Studies were conducted in Asia, Australasia, Europe, and North America. A range of hygiene and emollient interventions were assessed: a moisturising soap bar; combinations of water soak, oil soak, and lotion; regular application of a commercially available moisturiser; use of two different standardised skin care regimens comprising a body wash and leave-on body lotion; bed bath with "wash gloves" containing numerous ingredients; and application of a hot towel after usual care bed bath. In five studies, treatment duration ranged from five days to six months; only one study had post-treatment follow-up (one to eight days from end of treatment). Outcomes in the hot towel study were measured 15 minutes after the skin was wiped with a dry towel. Three studies each had high risk of attrition, detection, and performance bias. Only one trial (n = 984) assessed frequency of skin damage via average monthly incidence of skin tears during six months of treatment. The emollient group (usual care plus twice-daily application of moisturiser) had 5.76 tears per month per 1000 occupied bed-days compared with 10.57 tears in the usual care only group (ad hoc or no standardised skin-moisturising regimen) (P = 0.004), but this is based on very low-quality evidence, so we are uncertain of this result. Only one trial (n = 133) reported measuring side effects. At 56 ± 4 days from baseline, there were three undesirable effects (itch (mild), redness (mild/moderate), and irritation (severe)) in intervention group 1 (regimen consisting of a moisturising body wash and a moisturising leave-on lotion) and one event (mild skin dryness) in intervention group 2 (regimen consisting of body wash and a water-in-oil emulsion containing emollients and 4% urea). In both groups, the body wash was used daily and the emollient twice daily for eight weeks. There were zero adverse events in the usual care group. This result is based on very low-quality evidence. This same study also measured TEWL at 56 ± 4 days in the mid-volar forearm (n = 106) and the lower leg (n = 105). Compared to usual care, there may be no difference in TEWL between intervention groups, but evidence quality is low. One study, which compared application of a hot towel for 10 seconds after a usual care bed bath versus usual care bed bath only, also measured TEWL at 15 minutes after the skin was wiped with a dry towel for one second. The mean TEWL was 8.6 g/m²/h (standard deviation (SD) 3.2) in the hot towel group compared with 8.9 g/m²/h (SD 4.1) in the usual care group (low-quality evidence; n = 42), showing there may be little or no difference between groups. A lower score is more favourable. Three studies (266 participants) measured SCH, but all evidence is of very low quality; we did not combine these studies due to differences in treatments (different skin care regimens for eight weeks; wash gloves for 12 weeks; and single application of hot towel to the skin) and differences in outcome reporting. All three studies showed no clear difference in SCH at follow-up (ranging from 15 minutes after the intervention to 12 weeks from baseline), when compared with usual care. A clinical score of dryness was measured by three studies (including 245 participants); pooling was not appropriate. The treatment groups (different skin care regimens for eight weeks; a moisturising soap bar used for five days; and combinations of water soak, oil soak, and lotion for 12 days) may reduce dryness compared to standard care or no intervention (results measured at 5, 8, and 56 ± 4 days after treatment was initiated). However, the quality of evidence for this outcome is low. Outcomes of erythema and clinical score of itch were not assessed in any included studies.
AUTHORS' CONCLUSIONS
Current evidence about the effects of hygiene and emollients in maintaining skin integrity in older people in residential and hospital settings is inadequate. We cannot draw conclusions regarding frequency of skin damage or side effects due to very low-quality evidence. Low-quality evidence suggests that in residential care settings for older people, certain types of hygiene and emollient interventions (two different standardised skin care regimens; moisturising soap bar; combinations of water soak, oil soak, and lotion) may be more effective in terms of clinical score of dryness when compared with no intervention or standard care. Studies were small and generally lacked methodological rigour, and information on effect sizes and precision was absent. More clinical trials are needed to guide practice; future studies should use a standard approach to measuring treatment effects and should include patient-reported outcomes, such as comfort and acceptability.
Topics: Administration, Topical; Aged; Aged, 80 and over; Emollients; Female; Humans; Hygiene; Male; Patient Satisfaction; Pruritus; Randomized Controlled Trials as Topic; Skin Care; Soaps; Wounds and Injuries
PubMed: 32006460
DOI: 10.1002/14651858.CD011377.pub2 -
Digestive Diseases and Sciences Jun 2023We conducted a systematic literature review to understand the evidence supporting treatment decisions for cholestatic pruritus associated with primary biliary...
BACKGROUND AND AIMS
We conducted a systematic literature review to understand the evidence supporting treatment decisions for cholestatic pruritus associated with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).
METHODS
Studies that enrolled ≥ 75% participants with PBC or PSC and reported ≥ 1 endpoint(s) related to efficacy, safety, health-related quality of life (HRQoL) or other patient-reported outcomes were included. Bias was assessed using the Cochrane risk of bias tool for randomised controlled trials (RCTs) and the Quality of Cohort studies tool for non-RCTs.
RESULTS
Thirty-nine publications were identified, covering 42 studies and six treatment classes (including investigational and approved products): anion-exchange resins, antibiotics (rifampicin/derivatives), opiates, selective serotonin reuptake inhibitors, fibrates, ileal bile acid transporter inhibitors and other agents not categorised in these six classes. Across studies, median sample size was small (n = 18), 20 studies were over 20 years old, 25 followed patients for ≤ 6 weeks, only 25 were RCTs. Pruritus was assessed using several different tools, with inconsistencies in their application. Cholestyramine, considered first-line therapy for moderate-severe cholestatic pruritus, was assessed in six studies (two RCTs) including 56 patients with PBC and 2 with PSC, with evidence of efficacy demonstrated in only three studies, among which, two RCTs were assessed as having a high risk of bias. Findings were similar for other drug classes.
CONCLUSIONS
There is a lack of consistent and reproducible evidence available on efficacy, impact on HRQoL, and safety of cholestatic pruritus treatments, leaving physicians to rely on clinical experience rather than evidence-based medicine for treatment selection.
Topics: Humans; Young Adult; Adult; Liver Cirrhosis, Biliary; Cholangitis, Sclerosing; Pruritus; Fibric Acids; Quality of Life
PubMed: 36933112
DOI: 10.1007/s10620-023-07862-z -
Cells Dec 2023Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent... (Review)
Review
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent and/or chronic course of inflammatory skin lesions with intense pruritus. Its pathophysiologic features include barrier dysfunction, aberrant immune cell infiltration, and alterations in the microbiome that are associated with genetic and environmental factors. There is a complex crosstalk between these components, which is primarily mediated by cytokines. Epidermal barrier dysfunction is the hallmark of AD and is caused by the disruption of proteins and lipids responsible for establishing the skin barrier. To better define the role of cytokines in stratum corneum lipid abnormalities related to AD, we conducted a systematic review of biomedical literature in PubMed from its inception to 5 September 2023. Consistent with the dominant T2 skewness seen in AD, type 2 cytokines were featured prominently as possessing a central role in epidermal lipid alterations in AD skin. The cytokines associated with T1 and T17 were also identified to affect barrier lipids. Considering the broad cytokine dysregulation observed in AD pathophysiology, understanding the role of each of these in lipid abnormalities and barrier dysfunction will help in developing therapeutics to best achieve barrier homeostasis in AD patients.
Topics: Humans; Dermatitis, Atopic; Cytokines; Epidermis; Skin; Lipids
PubMed: 38132113
DOI: 10.3390/cells12242793 -
Life (Basel, Switzerland) Nov 2021Atopic dermatitis (AD) is a chronic inflammatory disease of the skin whose main symptom is pruritus and may affect all age ranges. Regarding the prevalence, it has been... (Review)
Review
Atopic dermatitis (AD) is a chronic inflammatory disease of the skin whose main symptom is pruritus and may affect all age ranges. Regarding the prevalence, it has been estimated at around 10% of the world population. Many concomitant diseases have been associated with AD, but the causal relationship between AD and psychological impairment has not been clearly established. Scientific literature studying the probable association between male or female sexual dysfunction and dermatological pathology is limited, even more so in AD. This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines and the Cochrane Collaboration methodology for systematic reviews. All relevant articles in English were identified through a search from inception to 10 December 2020, including the following databases: Medline (via PubMed), Scopus, Web of Science Core Collection, and SciELO. The results of the search were compiled using the COVIDENCE software for systematic reviews. The methodological quality of the included studies was done using the "Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies" and the "Quality Assessment of Case-Control Studies" developed by the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH). Our search yielded potentially relevant studies. Five studies that evaluated the prevalence of sexual dysfunction in atopic dermatitis were retrieved after applying the selection criteria. The present systematic review achieved data from 8088 patients with atopic dermatitis from four articles. Sample sizes for atopic dermatitis patients ranged from 266 to 3997. We identified one cohort study with four years of follow-up, three studies with a cross-sectional design, and one case-control study. Three studies reported data disaggregated by the severity of atopic dermatitis. Two studies included healthy controls with a total sample size of 1,747,755 subjects. Two studies compared data with other dermatological conditions such as psoriasis. In conclusion, we can establish that unlike other psychological comorbidities such as anxiety and depression, sexual dysfunction is a field scarcely explored in the literature. This sexual dysfunction focuses on the male sex in large population studies and in clinical diagnoses without exploring it through specific and validated questionnaires in this regard. Further studies focused on both genders are needed. It is important to correlate this sexual dysfunction with the severity of the disease, previous treatments, and cardiovascular comorbidities.
PubMed: 34947845
DOI: 10.3390/life11121314 -
Frontiers in Pharmacology 2022Pruritus is a common complication in patients with primary biliary cholangitis (PBC). The pathogenesis is not clear, and also the precise therapeutic measures remain...
Pruritus is a common complication in patients with primary biliary cholangitis (PBC). The pathogenesis is not clear, and also the precise therapeutic measures remain alluring. In order to systematically evaluate the efficacy and safety of drug interventions in the treatment of pruritus associated with PBC, this systemic review and meta-analysis was conducted. The randomized controlled trials (RCTs) on drug interventions in the treatment of pruritus associated with primary cholangitis were searched in the electronic databases of PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov. Two researchers independently screened the literature, extracted and integrated the data, and assessed the bias risk of the selected literature, according to the . Finally, the STATA 15.0 software was used for the meta-analysis. A total of 23 RCTs involving 2,194 patients were studied, that included 12 pharmacological interventions. In terms of itching relief, compared with placebo, UDCA, methotrexate and GSK2330672 had a definite effect in improving pruritus (pruritus remission rate before and after treatment, 0.05). In terms of serum indexes, compared with placebo group, UDCA, OCA, rifampicin, cyclosporine, NGM282, seladelpar and colchicine may improve blood alkaline phosphatase (ALP) ( 0.05), but only rifampicin showed low heterogeneity. UDCA, bezafibrate, OCA, rifampicin, NGM282 and others may improve blood γ-glutamyl transpeptidase (γ-GGT) ( 0.05), but due to the high heterogeneity and the limitation of research samples, a clear conclusion cannot be drawn. In terms of adverse events, except high (>15 mg/kg/day) and low doses (<13 mg/kg/day) of UDCA increased the incidence of adverse events, there were no risk of increasing the incidence of adverse events compared with placebo ( 0.05), and a moderate dose of UDCA (13-15 mg/kg/day) and malotilate (1,500 mg/day) may also help in reducing the incidence of adverse events ( 0.05). UDCA, methotrexate and GSK2330672 may relieve itching in patients with PBC, but there is a lack of robust evidence to support their effect on ALP or γ-GGT. Due to the heterogeneity in the published studies, based on the present review, we cannot explicitly recommend any specific drug for the treatment of PBC-related pruritus. link-https://osf.io/2g8ya, identifier 10.17605/OSF.IO/2G8YA.
PubMed: 36339545
DOI: 10.3389/fphar.2022.835991 -
Archives of Academic Emergency Medicine 2022Knowledge of the safety of vaccines is crucial, both to prevent and cure them and to decrease the public hesitation in receiving vaccines. Therefore, this study aimed to... (Review)
Review
INTRODUCTION
Knowledge of the safety of vaccines is crucial, both to prevent and cure them and to decrease the public hesitation in receiving vaccines. Therefore, this study aimed to systematically review the adverse events reported for inactivated vaccines and Novavax.
METHODS
In this systematic review, the databases of PubMed, Scopus, Cochrane, and Web of Science were searched on September 15, 2021. Then we identified the eligible studies using a two-step title/abstract and full-text screening process. Data on the subjects, studies, and types of adverse events were extracted and entered in a word table, including serious, mild, local, and systemic adverse events as well as the timing of side effects' appearance.
RESULTS
Adverse effects of inactivated coronavirus vaccines side effects were reported from phases 1, 2, and 3 of the vaccine trials. The most common local side effects included injection site pain and swelling, redness, and pruritus. Meanwhile, fatigue, headache, muscle pain, fever, and gastrointestinal symptoms including abdominal pain and diarrhea were among the most common systemic adverse effects.
CONCLUSION
This systematic review indicates that inactivated COVID-19 vaccines, including Sinovac, Sinopharm, and Bharat Biotech, as well as the protein subunit vaccines (Novavax) can be considered as safe choices due to having milder side effects and fewer severe life-threatening adverse events.
PubMed: 36033990
DOI: 10.22037/aaem.v10i1.1585 -
Heliyon Nov 2023In recent years, biologics targeting key cytokines and Janus kinase (JAK) inhibitors have demonstrated favorable efficacy and safety outcomes for atopic dermatitis (AD)...
BACKGROUND
In recent years, biologics targeting key cytokines and Janus kinase (JAK) inhibitors have demonstrated favorable efficacy and safety outcomes for atopic dermatitis (AD) therapy. To evaluate the short-term efficacy and safety of AD therapy involving biologics, JAK inhibitors, and their combination with topical corticosteroids (TCS) for patients with AD, we conducted this systematic review and meta-analysis. Using eligible randomized clinical trials (RCTs) of 12 or 16 weeks of treatment with systemic medications and 4 weeks of topical treatment for AD.
METHODS
PubMed, Web of Science, ScienceDirect, and the Cochrane Library were searched from inception up to October 25, 2023. English-language randomized clinical trials (RCTs) of 12 or 16 weeks of treatment with systemic medications and 4 weeks of topical treatment for AD were included. Titles, abstracts, and articles were screened in duplicate. Of 7261 citations, 37 studies were included. The data were analyzed using Review Manager 5.4 and the outcomes were measured by the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), the pruritus Numerical Rating Scale (NRS), as well as instances of adverse events (AE), and serious AE (SAE), which were presented as risk ratio (RR) with a 95 % confidence interval (CI). The efficacy of the biological therapies was analyzed with the percentage of patients who have achieved EASI 75, EASI 90, IGA 0/1 and pruritus NRS4, while the safety of treatments was evaluated in terms of the number of patients who had ≥1 AE and who had at least one SAE.
RESULTS
A total of 37 studies with 43 cohorts that examined 9 medications and placebo and involved 18172 participants were included. Compared with the placebo, all biologics and JAK inhibitors were associated with a higher response rate in efficacy outcomes, while systematic administration was presented by dupilumab 200 mg subcutaneously every 2 weeks with superior improvement in EASI 90 (RR 9.50, 95 % CI 2.31-39.03) and IGA0/1 (RR 17.00, 95 % CI 2.33-123.78), upadacitinib 30 mg once daily in EASI 75 (RR 5.14, 95 % CI 4.20-6.31) and Pruritus NRS4 (RR 5.73, 95 % CI 4.44-7.39), and external use was presented by ruxolitinib 1.5 % twice daily orally in EASI 75 (RR 4.14, 95 % CI 3.06-5.61) and Pruritus NRS4 (RR 4.08, 95 % CI 2.86-5.81), and most of doses led to a better safety profile. Most doses of baricitinib, dupilumab, tralokinumab, and upadacitinib in combination with TCS demonstrated good efficacy as compared with the control groups (placebo + TCS). However, patients receiving baricitinib at a dosage of 2 mg daily (RR 1.23, 95 % CI 1.02-1.49) and 4 mg daily (RR 1.39, 95 % CI 1.22-1.58) in combination with TCS, exhibited a higher incidence of one or more SAE as compared with those taking placebo + TCS.
CONCLUSION
Our research has revealed that ruxolitinib and dupilumab are effective and safe treatments for mild to moderate AD and moderate to severe AD, respectively. Additionally, the combination of dupilumab and TCS demonstrates greater efficacy and safety compared to baricitinib, tralokinumab, and upadacitinib with TCS as a background treatment for moderate to severe AD. We suggest that the use of topical JAK inhibitors could be a potential alternative to TCS when used in combination with systemic medications, as a novel approach to treat AD. Insufficient different data sources caused by partial interventions were only mentioned in a few articles and low event rates in safety analyses may lead to the results being biased. Further studies directly comparing existing and novel treatments are needed and will be included in forthcoming updates of this review. Our findings could form a useful foundation for developing a new generation of treatment guidelines for AD.
PubMed: 38034798
DOI: 10.1016/j.heliyon.2023.e22014 -
Dermatology (Basel, Switzerland) 2022Chronic nodular prurigo (CNPG) is a chronic, inflammatory skin disease, characterized by intense and debilitating pruritus. The pathophysiology is not fully understood,... (Review)
Review
BACKGROUND
Chronic nodular prurigo (CNPG) is a chronic, inflammatory skin disease, characterized by intense and debilitating pruritus. The pathophysiology is not fully understood, and the condition is difficult to treat with no targeted therapies. The aim of this systematic review was to review the evidence of therapies for non-atopic CNPG and conduct a meta-analysis of the results.
SUMMARY
We conducted a systematic review of the literature concerning effect of treatment for non-atopic CNPG. Due to few randomized controlled trials (RCTs) and case series, the literature was unfortunately too sparse to conduct a meta-analysis of the results. Instead, we thoroughly report important data from the three existing RCTs and 6 case studies with more than 15 patients. Evaluated therapies include nemolizumab, aprepitant, topical therapy with hydrocortisone and pimecrolimus, thalidomide, UVA phototherapy, pregabalin, and naltrexone. Included RCTs and case studies all had a heterogeneous methodology making direct comparison almost impossible.
KEY MESSAGES
There is sparse evidence for the currently used therapies for non-atopic CNPG. Several RCTs on new therapies are running or in the pipeline, hopefully providing new, effective, and targeted treatment possibilities for CNPG patients both with and without an atopic predisposition.
Topics: Chronic Disease; Graft vs Host Disease; Humans; Hypersensitivity, Immediate; Prurigo; Pruritus; Skin; Thalidomide; Ultraviolet Therapy
PubMed: 35417906
DOI: 10.1159/000523700 -
Frontiers in Immunology 2024Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined...
BACKGROUND
Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined evidence of Janus kinase inhibitors (JKIs) in atopic dermatitis (AD) is urgent.
METHODS
Six databases were searched for MAs published until October 2023. Qualitative description of MAs was mainly used, and Investigator's Global Assessment response (IGA response), the 75% improvement in Eczema Area and Severity Index (the EASI75), peak pruritus Numerical rating score (PP-NRS), and adverse effects were cited to describe the efficacy and safety of JKIs. The methodological quality of the included MAs was assessed by A Measurement Tool to Assess Systematic Reviews II (AMSTAR II), and the quality of evidence was evaluated by the grading of recommendations, assessment, development, and evaluation (GRADE).
RESULTS
Sixteen MAs were pooled in this review, of which five studies appraised JKIs, five appraised systemic JKIs, five papers assessed abrocitinib only, and one assessed baricitinib. Two studies were of "high" methodological quality and 14 MAs were of "moderate" quality. Eleven MAs integrated the results of JKIs and reported that JKIs provide faster onset of IGA response (RR=2.83, 95% CI [2.25, 3.56], high-quality evidence). Similarly, 10 MAs showed that JAK inhibitors were more effective in improving the EASI75 (RR=2.84, 95% CI [2.2, 3.67], high-quality evidence). Results from 12 MAs showed JKIs were active in reducing the PP-NRS (SMD=-0.49, 95% CI [-0.67, -0.32]). All MAs affirmed JKIs added no adverse effects leading to discontinuation and serious adverse events (P<0.05). However, 200mg of abrocitinib had a higher risk of acne (RR=4.34, 95% CI [1.61, 11.71), herpes zoster (RR=1.64, 95% CI [0.42, 6.39]), headache (RR=1.76, 95% CI [1.03, 3]), and nausea (RR=7.81, 95% CI [3.84, 15.87]). Upadacitinib was known to increase acne (RR=6.23, 95% CI [4.08, 9.49]), nasopharyngitis (RR=1.36, 95% CI [1.03, 1.8]) and blood creatine phosphokinase (blood CPK) (RR=2.41, 95% CI [1.47, 3.95]). Baricitinib at 2mg was associated with increased blood CPK (RR=2.25, 95% CI [1.1, 2.97]).
CONCLUSION
Compared to placebo or dupilumab, the administration of JKIs can ameliorate IGA response more effectively, improve the EASI75, and relieve pruritus without severe adverse effect, while accompanied by more acne, nasopharyngitis, headache, and digestive disturbances. The curative effect of 200 mg of abrocitinib is significant and more caution should be given in patients with gastrointestinal dysfunction, herpes zoster, and those who are acne-prone. Baricitinib and upadacitinib should be avoided in populations at high risk for cardiovascular events.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369369, PROSPERO (CRD42022369369).
Topics: Humans; Dermatitis, Atopic; Janus Kinase Inhibitors; Nasopharyngitis; Pruritus; Acne Vulgaris; Headache; Herpes Zoster; Immunoglobulin A; Purines; Sulfonamides; Pyrazoles; Pyrimidines; Azetidines
PubMed: 38464512
DOI: 10.3389/fimmu.2024.1342810 -
International Journal of Surgery... Jun 2023Available evidence shows that the incidence of toxicities associated with cancer immunotherapy, such as programmed cell death 1 (PD-1) and programmed cell death 1 ligand... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Available evidence shows that the incidence of toxicities associated with cancer immunotherapy, such as programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1)-related toxicities, is estimated to be between 0.3 and 1.3%.
OBJECTIVE
This systematic review aimed to investigate cancer patients' susceptibility to toxicities associated with PD-1/PD-L1 inhibitors and establish a clinically relevant landscape of side effects of PD-1/PD-L1 inhibitors.
DATA SOURCES
Relevant publications from PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI) between 2014 and 2019.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
We searched randomized controlled trials (RCTs) reporting treatment-related toxicities associated with PD-1 and PD-L1 inhibitors in the treatment of cancers. The primary endpoint was to assess the difference in the incidences of toxicities between cancer patients who did and did not receive PD-1/PD-L1 inhibitors. A total of 29 RCTs, incorporating 8576 patients, met the eligibility criteria.
STUDY APPRAISAL AND SYNTHESIS METHODS
We calculated the pooled relative risks and corresponding 95% CIs using a random-effects model and assessed the heterogeneity between different groups. The subgroup analyses were conducted based on cancer type, toxicity grade (severity), system and organ, treatment regimens in the intervention arm and the control arm, PD-1/PD-L1 inhibitor drug type, and cancer type.
RESULTS
A total of 11 categories (e.g. endocrine toxicity), and 39 toxicity types (e.g. hyperthyroidism) were identified. For toxicities at any grade, those treated with PD-1/PD-L1 inhibitors were at lower risks for gastrointestinal toxicity, hematologic toxicity, and treatment event leading to discontinuation; and were at higher risks for respiratory toxicity (all P <0.05). Those treated with PD-1/PD-L1 inhibitors were at lower risks for fatigue, asthenia, and peripheral edema and were at higher risks for pyrexia, cough, dyspnea, pneumonitis, and pruritus.
LIMITATIONS
The present research is a meta-analysis at the study level rather than at the patient level; insights on risk factors associated with the development of toxicities cannot be found in our study. There was a possible overlap in Common Terminology Criteria for Adverse Events (CTCAE) definitions which prevents understanding the true rates of specific toxicities.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
For most toxicity types based on system and organ, the incidence proportions for patients in the intervention arm were lower than those in the control arm, which suggested the general safety of PD-1/PD-L1 inhibitors against conventional chemotherapy and cytotoxic t-lymphocyte-associated protein 4 (CTLA-4) inhibitors. Future research should focus on taking effective targeted measures to decrease the risks of different toxicities for different patient populations.
SYSTEMATIC REVIEW REGISTRATION NUMBER
We registered the research protocol with PROSPERO (registration number CRD42019135113).
Topics: Humans; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Neoplasms; Risk; Incidence
PubMed: 37132038
DOI: 10.1097/JS9.0000000000000368