Safety of Systemic Agents for the Treatment of Pediatric Psoriasis.
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ABSTRACT:
SUBMITTER: Bronckers IMGJ
PROVIDER: S-EPMC5710436 | biostudies-other | 2017 Nov
REPOSITORIES: biostudies-other
Publications
Safety of Systemic Agents for the Treatment of Pediatric Psoriasis.
Bronckers Inge M G J IMGJ Seyger Marieke M B MMB West Dennis P DP Lara-Corrales Irene I Tollefson Megha M Tom Wynnis L WL Hogeling Marcia M Belazarian Leah L Zachariae Claus C Mahé Emmanuel E Siegfried Elaine E Philipp Sandra S Szalai Zsuzsanna Z Vleugels Ruth Ann RA Holland Kristen K Murphy Ruth R Baselga Eulalia E Cordoro Kelly K Lambert Jo J Alexopoulos Alex A Mrowietz Ulrich U Kievit Wietske W Paller Amy S AS
JAMA dermatology 20171101 11
<h4>Importance</h4>Use of systemic therapies for moderate to severe psoriasis in children is increasing, but comparative data on their use and toxicities are limited.<h4>Objective</h4>To assess patterns of use and relative risks of systemic agents for moderate to severe psoriasis in children.<h4>Design, setting, and participants</h4>A retrospective review was conducted at 20 centers in North America and Europe, and included all consecutive children with moderate to severe psoriasis who used syst ...[more]
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Project description:Background Biological agents have been used with extreme caution in children because of their possible adverse effects. Objectives This study used high-quality randomized controlled trials (RCTs) to provide high-level evidence to assess the effectiveness and safety of biological agents for treating children with psoriasis. Methods We searched PubMed, Embase, Cochrane, and Web of Science databases through October 31, 2021. We included trials reporting at least one adverse event after treatment with biological agents of patients less than 18-year-old diagnosed with psoriasis. RevMan 5.3 and Stata 15.0 software were used for meta and Bayesian analyses. Results Six trials with 864 participants were included in the analysis. The results showed a 2.37-fold higher response rate in all biologics groups than in the control group for psoriasis area and severity index 75 (PASI75) (RR= 2.37, P-value < 0.01, 95% confidence interval [CI] [1.22, 4.62]). Compared with placebo, the PASI75 response rates of etanercept (RR= 2.82, 95% [CI] [1.10, 7.21]), ustekinumab low dose (RR= 7.45, 95%[CI] [1.25, 44.58]), and ustekinumab high dose (RR= 7.25, 95%[CI] [1.21, 43.41]) were superior. Additionally, the incidence of total adverse reactions was 1.05 times higher for biologics than for controls, indicating a good safety profile (RR= 1.05, P-value = 0.53, 95%[CI] [0.92, 1.19]). Overall, these six high-quality randomized controlled trials suggest that biologics are effective and safe for pediatric patients with psoriasis. Limitations Inclusion of few relevant, high-quality RCTs. Conclusion The results of this study indicate that biologics can be used to treat children with moderate-to-severe psoriasis without the risk of adverse effects. Ustekinumab showed the best efficacy and the fewest adverse effects.
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Project description:BackgroundTo determine the safety and efficacy of biological agents used in the treatment of systemic lupus erythematosus (SLE) in adults.MethodsSystematic review and meta-analysis following PRISMA guidelines.Data sourcesMEDLINE (through Pubmed), EMBASE, Cochrane library, Clinicaltrials.gov, Australianclinicaltrials.gov.au, ANZCTR.org.au and WHO International Clinical Trials Registry Platform for studies published from 20 May 2021 and 15 years prior. A grey literature search was performed and completed on 31 May 2021.Study criteriaPhase II, III or quasi randomised controlled trials, studies with only cerebral or cutaneous lupus were excluded.Data extractionTwo authors independently screened studies for eligibility, extracted, reviewed data for accuracy, and used the Cochrane tool to assess risk of bias.ResultsForty-four studies were identified, consisting of 15 groups of drugs and 25 different biological agents, totalling 16,889 patients. The main outcomes assessed included Systemic Lupus Erythematosus Responder Index (SRI), BILAG-Based Composite Lupus Assessment (BICLA) and combined combined/partial renal remission (CRR/PRR). Four groups of biologics were found to improve outcomes. Anti-interferons: Anifrolumab increased BICLA response and SRI 5 to 8, decreased prednisone dosages, with increased herpes zoster infections, but fewer serious adverse events. Sifalimumab improved SRI but also increased herpes zoster infections. Anti BAFF/BLyS and/or APRIL: Belimumab consistently improved SRI 4, decreased prednisone dosages, increased combined CRR/PRR, and had no adverse safety outcomes. Tabalumab increased SRI 5 at 52 weeks with no steroid sparing effect but was associated with increased infusion related adverse events. Telitacicept improved SRI 4 at 52 weeks, with no increased adverse events, though data was rather sparse. Anti CD-20 monoclonal antibody, Obinutuzumab increased combined CRR/PRR at 1 and 2 years. Anti IL12/23 monoclonal antibody, Ustekinumab, increased SRI 4 to 6, but not BICLA at 24 weeks, with no concerning safety outcomes.ConclusionMultiple biologic agents are shown in high quality studies to have a significant therapeutic impact on outcomes in SLE.
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Project description:Aggregate data model-based meta-analysis is a regression approach to compare the dose-response and/or time-course across different treatments using summary level data from the literature. Literature search and systematic review following the Cochrane approach yielded 912 sources for investigational and approved treatments for psoriasis. In addition, data for tofacitinib were obtained from an internal database. Tofacitinib is an oral Janus kinase inhibitor. Two mathematical models were developed for Psoriasis Area and Severity Index (PASI) response in moderate to severe psoriasis patients to quantify the time to maximum effect for PASI75 and to evaluate the dose-response relationship for PASI responders (PASI50, PASI75, PASI90, PASI100) at Week 12. Body weight exhibited an inverse effect on the placebo component of both models, suggesting that body weight affects the overall PASI response regardless of drug. This analysis provides a quantitative framework for efficacy comparisons across psoriasis treatments.
| S-EPMC5697570 | biostudies-literature
Project description:Background: Antibiotics are considered the backbone of rosacea management, especially for controlling inflammatory papules and pustules. We aim to evaluate the efficacy and safety of varied prescriptions and doses of antibiotics in treating rosacea by network meta-analysis. Methods: In this study, we compared all available randomized controlled trials (RCTs) that have studied systemic and topical antibiotics and placebo in rosacea therapy. We searched databases such as the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PubMed, Web of Science, and LILACS for published and unpublished RCTs on ClinicalTrials.gov before April 2023. The primary outcome was the improvement of the Investigator's Global Assessment (IGA) scores, and the secondary outcomes consisted of the improvement of the Patient's Global Assessment (PaGA) scores, Clinician's Erythema Assessment (CEA) scores, and adverse events (AEs). We used Bayesian random effects models for multiple treatment comparisons. Results: We identified 1,703 results through these databases. Thirty-one randomized trials with 8,226 patients were included. The heterogeneity and inconsistency between the trials were low, with a low risk of bias of all trials. Oral doxycycline 40 mg, minocycline 100 mg, and minocycline 40 mg, as well as topical ivermectin and metronidazole 0.75%, were effective in treating papules and pustules, thereby decreasing IGA in rosacea. Among these, minocycline 100 mg ranked top in efficacy. As for improving the PaGA scores, topical ivermectin, metronidazole 1%, and systemic oxytetracycline were effective, of which oxytetracycline worked the best. Both doxycycline 40 mg and metronidazole 0.75% presented no therapeutic effect for erythema. Considering the safety of the agents, systemic application of azithromycin and doxycycline 100 mg significantly increase the risk of AEs. Conclusion: Our review suggests that a high dosage of systemic minocycline is the most effective in treating rosacea phenotypes with papules and pustules with a low risk of AEs. However, there were no sufficient evidence-based data in exploring the influence of antibiotics on erythema. The phenotype of rosacea should be taken into consideration along with benefit and safety when making prescriptions due to AEs. Clinical Trial Registration: NCT(2016): http://cochranelibrary-wiley.com/o/cochrane/clcentral/articles/962/CN-01506962/frame.html NCT(2017): http://cochranelibrary-wiley.com/o/cochrane/clcentral/articles/764/CN-01565764/frame.html.
| S-EPMC10210163 | biostudies-literature
Project description:ImportanceFew studies have compared the use of methotrexate and biologics, the most commonly used systemic medications for treatment of moderate to severe psoriasis in children.ObjectiveTo assess the real-world, 6-month reduction in psoriasis severity and long-term drug survival (rate and duration of adherence to a specific drug) of methotrexate vs biologics in plaque psoriasis in children.Design, setting, and participantsA retrospective medical records review was conducted at 20 European and North American centers. Treatment response was based on site-reported Psoriasis Area and Severity Index (PASI) and/or Physician Global Assessment (PGA) scores at baseline and within the first 6 months of treatment. Participants included all 234 consecutively seen children with moderate to severe psoriasis who received at least 3 months of methotrexate or biologics from December 1, 1990, to September 16, 2014, with sufficient data for analysis. Data analysis was performed from December 14, 2015, to September 1, 2016.Main outcomes and measuresPASI, with a range from 0 to 72 (highest score indicating severe psoriasis), and/or PGA, with a scale of 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), and 5 (very severe).ResultsOf 234 pediatric patients (103 boys [44.0%]; 131 girls [56.0%]) treated with methotrexate and/or biologics, 163 patients (69.7%) exclusively received methotrexate, 47 patients (20.1%) exclusively received biologics, and 24 children (10.2%) received methotrexate and biologics sequentially. Of the latter cohort, 23 children were treated initially with methotrexate. Mean (SD) age at initiation was 11.6 (3.7) years for methotrexate and 13.3 (2.9) years for biologics (73.2% for etanercept) (P = .002). Among patients evaluated by a scoring method at 6-month follow-up, 75% or greater improvement in PASI (PASI75) was achieved in 12 of 30 patients (40.0%) receiving methotrexate and 20 of 28 patients (71.4%) receiving biologics, and PGA was clear/almost clear (PGA 0/1) in 41 of 115 patients (35.6%) receiving methotrexate and 18 of 37 patients (48.6%) receiving biologics. Achieving PASI75 and/or PGA 0/1 between baseline and 6 months was more likely with biologics than methotrexate (PASI75: odds ratio [OR], 4.56; 95% CI, 2.02-10.27; P < .001; and PGA 0/1: OR, 2.00; 95% CI, 0.98-4.00; P = .06). Decreased mean PASI and PGA scores were associated with biologics more than with methotrexate (PASI effect, -3.13; 95% CI, -4.33 to -1.94; P < .001; and PGA effect, -0.31; 95% CI, -0.56 to -0.06; P = .02). After 1, 3, and 5 years of use, overall drug survival rates for methotrexate were 77.5%, 50.3%, and 35.9%, and for biologics, the rates were 83.4%, 64.3%, and 57.1%, respectively. Biologics were associated with a better confounder-corrected drug survival than methotrexate (hazard ratio [HR], 2.23; 95% CI, 1.21-4.10; P = .01). Discontinuation owing to lack of response was comparable (HR, 1.64; 95% CI, 0.80-3.36; P = .18).Conclusions and relevanceMethotrexate and biologics appear to be associated with improvement in pediatric psoriasis, although biologics seem to be associated with greater reduction in psoriasis severity scores and higher drug survival rates than methotrexate in the real-world setting. Additional studies directly comparing these medications should be performed for confirmation.
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Project description:Psoriasis is a chronic inflammatory systemic disease primarily affecting the skin, but which often involves considerable comorbidities as well. One-third of psoriasis cases start during childhood. In pediatric psoriasis, an association with several medical comorbidities is also indicated. Furthermore, because of its chronic nature and frequent relapses, psoriatic patients tend to require long-term treatment and experience negative impacts on their quality of life. Considering the different clinical characteristics of pediatric psoriasis, it has recently been presented that the pathogenesis of pediatric psoriasis is distinct from adult psoriasis. Treatment for pediatric psoriasis usually involves the same methods as for adults. However, most treatments in pediatric psoriasis are used off-label and research in this regard is still lacking. Targeted therapies involving newly developed biologics are also increasingly being applied to psoriasis in children. This review summarizes the clinical characteristics of pediatric psoriasis and focuses mainly on the updated concepts of pathogenesis and treatments in pediatric psoriasis. This was undertaken to widen the understanding of these relevant aspects and to provide better management of pediatric psoriasis by clinicians.
| S-EPMC8393839 | biostudies-literature
Project description:BackgroundPsoriasis is a chronic inflammatory skin disease induced by autoimmune-like dysregulation of the immune system. Treatment options have drastically evolved in recent years, and treatment advances that target specific cytokines and other molecules involved in dysregulation have had a profound effect in controlling the disease.ObjectiveWe reviewed the literature to assess the risk of developing melanoma with conventional therapies and newer agents used to treat psoriasis.MethodsA comprehensive literature search using Medline (via Ovid) and Embase was conducted.ResultsThe majority of studies reviewed reported insignificant results. Potential risk for melanoma was identified for only 3 out of 15 anti-psoriatic treatments analyzed: adalimumab (relative risk 1.8, 95% CI 1.06-3.00), etanercept (relative risk 2.35, 95% CI 1.46-3.77) and infliximab (Empirical Bayes Geometric Mean 7.90, 95% CI 7.13-8.60). The confidence intervals provided are from prior studies. There are not enough collective data on newer agents to make any conclusions on risk.ConclusionsWe were unable to identify any substantial risk for developing melanoma due to the use of anti-psoriatic treatments. Until additional long-term registry data become available, it would be prudent to continue screening patients with psoriasis at baseline and periodically for melanoma when these agents are used.
| S-EPMC8750137 | biostudies-literature
Project description:BackgroundResponses to the systemic treatments commonly used to treat psoriasis vary. Biomarkers that accurately predict effectiveness and safety would enable targeted treatment selection, improved patient outcomes and more cost-effective healthcare.ObjectivesTo perform a scoping review to identify and catalogue candidate biomarkers of systemic treatment response in psoriasis for the translational research community.MethodsA systematic search of CENTRAL, Embase, LILACS and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving patients with psoriasis (any age, n ≥ 50) reporting biomarkers associated with systemic treatment response. The main outcomes were any measure of systemic treatment efficacy or safety. Data were extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multistakeholder group using a majority voting consensus exercise and mapped to relevant cellular and molecular pathways.ResultsOf 71 included studies (67 studying effectiveness outcomes and eight safety outcomes; four studied both), most reported genomic or proteomic biomarkers associated with response to biologics (48 studies). Methodological or reporting limitations frequently compromised the interpretation of findings, including inadequate control for key covariates, lack of adjustment for multiple testing, and selective outcome reporting. We identified candidate biomarkers of efficacy to tumour necrosis factor inhibitors [variation in CARD14, CDKAL1, IL1B, IL12B and IL17RA loci, and lipopolysaccharide-induced phosphorylation of nuclear factor (NF)-κB in type 2 dendritic cells] and ustekinumab (HLA-C*06:02 and variation in an IL1B locus). None were supported by sufficient evidence for clinical use without further validation studies. Candidate biomarkers were found to be involved in the immune cellular crosstalk implicated in psoriasis pathogenesis, most notably antigen presentation, T helper (Th)17 cell differentiation, positive regulation of NF-κB, and Th17 cell activation.ConclusionsThis comprehensive catalogue provides a key resource for researchers and reveals a diverse range of biomarker types and outcomes in the included studies. The candidate biomarkers identified require further evaluation in methodologically robust studies to establish potential clinical utility. Future studies should aim to address the common methodological limitations highlighted in this review to expedite discovery and validation of biomarkers for clinical use. What is already known about this topic? Responses to the systemic treatments commonly used to treat psoriasis vary. Biomarkers that accurately predict effectiveness and safety would enable targeted treatment selection, improved patient outcomes and more cost-effective healthcare. What does this study add? This review provides a comprehensive catalogue of investigated biomarkers of systemic treatment response in psoriasis. A diverse range of biomarker types and outcomes was found in the included studies, serving as a key resource for the translational research community.
| S-EPMC9796396 | biostudies-literature
Project description:BackgroundThe decision of when to discontinue systemic treatment after achieving remission in psoriasis is an important question. In this systematic review, we sought to evaluate time to relapse after the discontinuation of systemic treatment in psoriasis patients.MethodsSystematic searches of PubMed, Cochrane Library, and Embase databases were performed for randomized controlled studies reporting time to relapse after discontinuation of systemic drugs in psoriasis patients. In addition, pharmaceutical companies were contacted by the authors regarding missing data from the identified publications. In each publication, the time to psoriasis relapse and the timing of drug discontinuation were carefully assessed. The level of psoriasis control at the time of drug discontinuation and the definition used for psoriasis relapse were taken into account.ResultsThirty articles published before April 2021 were included in the systematic review. Four articles focused on conventional systemic treatments with methotrexate and/or cyclosporine, nine focused on tumor necrosis factor (TNF) antagonists, eight focused on interleukin-17 (IL-17) antagonists, eight focused on IL-12/23 or IL-23 antagonists, and one focused on tofacitinib and apremilast. Different definitions were used to define psoriasis treatment success at the time of drug discontinuation. Similarly, heterogeneous criteria were used to define psoriasis relapse. Comparison between drugs was performed indirectly (i.e. across studies) for most drugs. Considering time of 50% loss of maximum Psoriasis Area Severity Index (PASI) improvement, a shorter median time to psoriasis relapse was observed with traditional systemic treatment (~ 4 weeks) compared to biological agents (from 12 to ~ 34 weeks). When using stringent relapse criteria, such as loss of PASI 90, a longer time to relapse after treatment cessation was observed with IL-23 antagonists (21-42 weeks) versus IL-17 antagonists (7-24 weeks).ConclusionBiological agents are associated with a longer time to relapse than oral systemic agents after drug discontinuation. Among biologicals, IL-23 antagonists are associated with the longest time to relapse. These findings may have clinical consequences for the selection of systemic agents when intermittent treatment is necessary.
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