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American Journal of Clinical Dermatology Sep 2023Nail changes are frequent clinical findings in patients with cutaneous psoriasis and psoriatic arthritis, often causing significant impairments in quality of life....
INTRODUCTION
Nail changes are frequent clinical findings in patients with cutaneous psoriasis and psoriatic arthritis, often causing significant impairments in quality of life. Numerous targeted therapies have been previously studied for treatment of nail psoriasis, however, newer agents have not been captured in prior systematic reviews. With over 25 new studies published since 2020, the landscape of nail psoriasis systemic treatments is rapidly evolving, warranting analysis of recently approved therapies.
METHODS
An updated systematic review of all PubMed and OVID database studies assessing efficacy and safety of targeted therapies for nail psoriasis was performed, with the goal of incorporating clinical data of recent trials and newer agents, namely brodalumab, risankizumab, and tildrakizumab. Eligibility criteria included clinical human studies reporting at least one of the nail psoriasis clinical appearance outcomes (Nail Psoriasis Severity Index, modified Nail Psoriasis Severity Index).
RESULTS
A total of 68 studies on 15 nail psoriasis targeted therapeutic agents were included. Biological agents and small molecule inhibitors included TNF-alpha inhibitors (adalimumab, infliximab, etanercept, certolizumab, golimumab), IL-17 inhibitors (ixekizumab, brodalumab, secukinumab), IL-12/23 inhibitors (ustekinumab), IL-23 inhibitors (guselkumab, risankizumab, tildrakizumab), PDE-4 inhibitors (apremilast), and JAK inhibitors (tofacitinib). These agents all demonstrated statistically significant improvements in nail outcome scores, compared with placebo or with baseline values, at weeks 10-16 and weeks 20-26, with some studies assessing efficacy up to week 60. Safety data for these agents were acceptable and consistent with known safety profiles within these timepoints, with nasopharyngitis, upper respiratory tract infections, injection site reactions, headache, and diarrhea being the most reported adverse events. Specifically, the newer agents, brodalumab, risankizumab, and tildrakizumab, showed promising outcomes for treatment of nail psoriasis on the basis of current data.
CONCLUSION
Numerous targeted therapies have shown significant efficacy in improving nail findings in patients with psoriasis and psoriatic arthritis. Data from head-to-head trials have shown greater efficacy of ixekizumab over adalimumab and ustekinumab, as well as brodalumab over ustekinumab, while prior meta-analyses have demonstrated superiority of ixekizumab and tofacitinib to other included agents at various assessed timepoints. Further studies on the long-term efficacy and safety of these agents, as well as randomized controlled trials involving comparison with placebo arms, are needed to fully analyze differences in efficacy of newer agents compared with previously established therapies.
Topics: Humans; Ustekinumab; Adalimumab; Arthritis, Psoriatic; Quality of Life; Treatment Outcome; Psoriasis
PubMed: 37209391
DOI: 10.1007/s40257-023-00786-4 -
Advances in Therapy May 2023Dose escalation is one of the treatment approaches studied and suggested in advanced therapies for Crohn's disease (CD) and ulcerative colitis (UC). This study aimed to... (Review)
Review
INTRODUCTION
Dose escalation is one of the treatment approaches studied and suggested in advanced therapies for Crohn's disease (CD) and ulcerative colitis (UC). This study aimed to identify and characterize the dosing escalation patterns of advanced therapies in CD and UC.
METHODS
Two systematic literature reviews (SLRs) were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, Embase, and Cochrane Library were searched for articles published between January 2011 and October 2021 and limited to non-interventional studies in English language. Congress and bibliographic searches were also conducted. Articles were screened by two independent researchers. Dose escalation patterns were described and summarized considering the regional regulatory label recommendation (in North America [NA] or outside of North America [ONA]).
RESULTS
Among 3190 CD and 2116 UC articles identified in the Ovid searches, 100 CD and 54 UC studies were included in the SLR, with more studies conducted ONA. Most studies reported an initial maintenance dose pattern aligned with the lower starting dose per local regulatory label; however, several ONA studies (n = 13 out of 14) reported ustekinumab every 8 weeks as starting maintenance pattern in CD. In ONA studies, the median within-guideline escalation rates in CD and UC were 43% in ustekinumab (CD only), 33% and 32% for vedolizumab; 29% and 39% for adalimumab; and 14% and 10% for infliximab. Evidence regarding dose escalation patterns for tofacitinib, certolizumab pegol, and golimumab was limited. Some dose escalation patterns outside of label recommendations were observed including ustekinumab every 8 weeks to every 4 weeks and vedolizumab every 8 weeks to every 6 weeks.
CONCLUSION
Dose escalation strategies are widely documented in the literature. The reported dose escalation patterns and escalation rates vary by region and by CD and UC. Most escalation patterns reported were aligned with regulatory recommendations while some reported more diverse or aggressive dose escalation.
PROSPERO REGISTRATION
CRD42021289251.
Topics: Humans; Crohn Disease; Colitis, Ulcerative; Ustekinumab; Adalimumab; Infliximab
PubMed: 36930430
DOI: 10.1007/s12325-023-02457-6 -
JAMA Network Open May 2023Biosimilar drugs are potentially lower-cost versions of biologics that may improve access to therapy. However, there is a lack of adequate systematic reviews... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Biosimilar drugs are potentially lower-cost versions of biologics that may improve access to therapy. However, there is a lack of adequate systematic reviews demonstrating equivalence between these drugs for the treatment of rheumatoid arthritis (RA).
OBJECTIVES
To assess the efficacy, safety, and immunogenicity associated with biosimilars of adalimumab, etanercept, and infliximab compared with their reference biologics in patients with RA.
DATA SOURCES
MEDLINE via PubMed, Embase, Cochrane Central Register of Controlled Trials, and LILACS databases were searched from inception to September 2021.
STUDY SELECTION
Head-to-head randomized clinical trials (RCTs) of biosimilars of adalimumab, etanercept, and infliximab and their biologic reference drugs for RA were assessed.
DATA EXTRACTION AND SYNTHESIS
Two authors independently abstracted all data. Meta-analysis was conducted with bayesian random effects using relative risks (RRs) for binary outcomes and standardized mean differences (SMDs) for continuous outcomes, with 95% credible intervals (CrIs) and trial sequential analysis. Specific domains were assessed for the risk of bias in equivalence and noninferiority trials. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline.
MAIN OUTCOMES AND MEASURES
Equivalence was tested using prespecified margins for the American College of Rheumatology criteria, with at least 20% improvement in the core set measures (ACR20) (ie, RR, 0.94 to 1.06), and for the Health Assessment Questionnaire-Disability Index (HAQ-DI) (ie, SMD, -0.22 to 0.22). Secondary outcomes included 14 items measuring safety and immunogenicity.
RESULTS
A total of 25 head-to-head trials provided data on 10 642 randomized patients with moderate to severe RA. Biosimilars met equivalence with reference biologics in terms of ACR20 response (24 RCTs with 10 259 patients; RR, 1.01; 95% CrI, 0.98 to 1.04; τ2 = 0.000) and change of HAQ-DI scores (14 RCTs with 5579 patients; SMD, -0.04; 95% CrI, -0.11 to 0.02; τ2 = 0.002) considering prespecified margins of equivalence. Trial sequential analysis found evidence for equivalence for ACR20 since 2017 and HAQ-DI since 2016. Overall, biosimilars were associated with similar safety and immunogenicity profiles compared with reference biologics.
CONCLUSION AND RELEVANCE
In this systematic review and meta-analysis, biosimilars of adalimumab, infliximab, and etanercept were associated with clinically equivalent treatment effects compared with their reference biologics for the treatment of RA.
Topics: Humans; Etanercept; Adalimumab; Infliximab; Biosimilar Pharmaceuticals; Antirheumatic Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Arthritis, Rheumatoid
PubMed: 37234004
DOI: 10.1001/jamanetworkopen.2023.15872 -
Expert Review of Clinical Immunology 2023Palmoplantar psoriasis (PP) represents a localized type of disease. While controversy over its' classification exists, a hyperkeratotic type, a pustular type and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Palmoplantar psoriasis (PP) represents a localized type of disease. While controversy over its' classification exists, a hyperkeratotic type, a pustular type and palmoplantar pustulosis (PPP) have been recognized. PP management is regularly supported by biologic agents. Our study aimed to review and synthesize available data regarding the efficacy of approved biologics for PP and PPP.
RESEARCH DESIGN AND METHODS
A literature search was conducted in PubMed, CENTRAL, Scopus, and ClinicalTrilas.gov. Utilizing random-effects inverse-variance frequentist network meta-analyses (NMAs), we ranked interventions. The proportion of participants with cleared skin was the primary outcome. Fifty and 75% improvement in palmoplantar psoriasis area severity index (PPASI) were also explored (PPASI50, PPASI75).
RESULTS
In total, 15 randomized controlled trials (RCTs) exploring the efficacy of on-label adalimumab, bimekizumab, etanercept, guselkumab, infliximab, ixekizumab, secukinumab, and ustekinumab were included. Data for PP were synthesized. Every biologic agent examined, except from infliximab, outperformed placebo. On-label secukinumab exhibited the highest probability of inducing complete resolution. Ixekizumab and infliximab ranked best on inducing PPASI50 and PPASI75. Our review supports that guselkumab is effective for PPP.
CONCLUSIONS
Secukinumab, ixekizumab and infliximab are effective for PP. Research is warranted to produce evidence about the efficacy of biologics in PP and PPP.
Topics: Humans; Infliximab; Network Meta-Analysis; Biological Factors; Psoriasis; Biological Products; Severity of Illness Index; Treatment Outcome
PubMed: 37842734
DOI: 10.1080/1744666X.2023.2272049 -
Inflammatory Bowel Diseases Mar 2023The medical treatment of fistulizing Crohn's disease (CD) remains a challenge to clinicians. Over the last 20 years, biologic therapies have been the mainstay of medical... (Meta-Analysis)
Meta-Analysis
Comparative Efficacy of Biologic Therapies for Inducing Response and Remission in Fistulizing Crohn's Disease: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
BACKGROUND
The medical treatment of fistulizing Crohn's disease (CD) remains a challenge to clinicians. Over the last 20 years, biologic therapies have been the mainstay of medical treatment of fistulizing CD. The purpose of this study is to compare the efficacy of biologic therapies in inducing response and remission in fistulizing CD.
METHODS
We performed a systematic review of the EMBASE, MEDLINE, and Cochrane Central databases from inception to December 2021. Inclusion criteria were any randomized controlled trials (RCTs) that evaluated the efficacy of biologic therapies against an active comparator or placebo for induction of response or remission in adults with fistulizing CD. The proportion of patients with fistula response or remission, as defined by each clinical trial, was our primary study outcome. A Bayesian random-effects network meta-analysis was used to measure treatment effects and results were reported as odds ratio (OR) and 95% confidence interval (CI).
RESULTS
In our analysis, 10 studies were included, and all were RCTs. Infliximab was superior to adalimumab in inducing response (OR, 0.24; 95% CI, 0.06-0.99) but not in inducing remission (OR, 0.31; 95% CI, 0.04-2.27). Tumor necrosis factor antagonists were superior to placebo in the induction of response (OR, 0.51; 95% CI, 0.35-0.750) and remission (OR, 0.36; 95% CI, 0.22-0.58). Infliximab was superior to placebo in inducing response (OR, 0.36; 95% CI, 0.17-0.75) and remission (OR, 0.17; 95% CI, 0.03-0.87). Ustekinumab was superior to placebo in inducing response (OR, 0.48; 95% CI, 0.26-0.860) but not in inducing remission (OR, 0.50; 95% CI, 0.13-1.93). When comparing biologic therapies against each other, there was no statistical difference in inducing remission. Vedolizumab was not superior to placebo in inducing remission (OR, 0.32; 95% CI, 0.04-2.29). Certolizumab was not superior to placebo in inducing response (OR, 0.78; 95% CI, 0.40-1.55) or remission (OR, 0.78; 95% CI, 0.40-1.55).
CONCLUSIONS
Tumor necrosis factor antagonists are effective in inducing response and remission in fistulizing CD. Infliximab was superior to adalimumab for inducing response but not for inducing remission. Ustekinumab is effective in the induction of response but not in the induction of remission. When compared against each other, biologic therapies showed no significant difference in the induction of remission. Based on the available data, infliximab is the preferred first-line treatment. As for other biologics, the limited published data do not allow us to make firm recommendations. This study supports current practice and emphasizes the need for dedicated RCTs to evaluate the efficacy of biologic therapies in fistulizing CD.
Topics: Adult; Humans; Crohn Disease; Adalimumab; Infliximab; Ustekinumab; Tumor Necrosis Factor Inhibitors; Network Meta-Analysis; Randomized Controlled Trials as Topic; Biological Therapy; Remission Induction
PubMed: 35604382
DOI: 10.1093/ibd/izac103 -
Journal of the European Academy of... Jan 2019Hidradenitis suppurativa (HS)/acne inversa is a debilitating chronic disease that remains poorly understood and difficult to manage. Clinical practice is variable, and...
Hidradenitis suppurativa (HS)/acne inversa is a debilitating chronic disease that remains poorly understood and difficult to manage. Clinical practice is variable, and there is a need for international, evidence-based and easily applicable consensus on HS management. We report here the findings of a systematic literature review, which were subsequently used as a basis for the development of international consensus recommendations for the management of patients with HS. A systematic literature review was performed for each of nine clinical questions in HS (defined by an expert steering committee), covering comorbidity assessment, therapy (medical, surgical and combinations) and response to treatment. Included articles underwent data extraction and were graded according to the Oxford Centre for Evidence-based Medicine criteria. Evidence-based recommendations were then drafted, refined and voted upon, using a modified Delphi process. Overall, 5310 articles were screened, 171 articles were analysed, and 65 were used to derive recommendations. These articles included six randomized controlled trials plus cohort studies and case series. The highest level of evidence concerned dosing recommendations for topical clindamycin in mild disease (with systemic tetracyclines for more frequent/widespread lesions) and biologic therapy (especially adalimumab) as second-line agents (following conventional therapy failure). Good-quality evidence was available for the hidradenitis suppurativa clinical response (HiSCR) as a dichotomous outcome measure in inflammatory areas under treatment. Lower-level evidence supported recommendations for topical triclosan and oral zinc in mild-to-moderate HS, systemic clindamycin and rifampicin in moderate HS and intravenous ertapenem in selected patients with more severe disease. Intralesional or systemic steroids may also be considered. Local surgical excision is suggested for mild-to-moderate HS, with wide excision for more extensive disease. Despite a paucity of good-quality data on management decisions in HS, this systematic review has enabled the development of robust and easily applicable clinical recommendations for international physicians based on graded evidence.
Topics: Adalimumab; Anti-Bacterial Agents; Anti-Inflammatory Agents; Biological Products; Comorbidity; Consensus; Delphi Technique; Hidradenitis Suppurativa; Humans; Practice Guidelines as Topic; Smoking
PubMed: 30176066
DOI: 10.1111/jdv.15233 -
Autoimmunity Reviews Jun 2021The primary vasculitides constitute a heterogeneous group of immune mediated diseases of incompletely understood pathogenesis currently classified by the size of blood... (Review)
Review
The primary vasculitides constitute a heterogeneous group of immune mediated diseases of incompletely understood pathogenesis currently classified by the size of blood vessels affected (Chapel Hill classification). In recent years, several drugs with well-characterized immunological targets have been tested in clinical trials in large vessel vasculitis and small vessel vasculitis. Such trials provide "reverse translational" or bedside to bench information about underlying pathogenic mechanisms. Therefore, the aim of this systematic literature review was to examine the evidence base for a more refined mechanistic immunological classification of vasculitis. A total of 40 studies (20 randomized controlled trials (RCTs), 16 prospective studies, 1 retrospective cohort study and 3 case series) were included for full qualitative assessment. RCTs concerning biologic therapy for large vessel vasculitis mainly supports interleukin 6 receptor inhibition (tocilizumab). RCTs concerning biologic therapy for granulomatosis with polyangiitis and microscopic polyangiitis mainly support anti-CD20 treatment (rituximab) and complement inhibition with a small molecule C5a receptor antagonist (avacopan) is an emerging treatment option. The biologic treatment of eosinophilic granulomatosis with polyangiitis is centered around interleukin 5 inhibition (mepolizumab). Studies on tumor necrosis factor alpha inhibition (adalimumab, infliximab, and etanercept) showed negative results in giant cell arteritis but some effect in Takayasu arteritis. Taken together, clinical studies with cytokine and cell specific drugs are dissecting the heterogeneous immunopathogenic mechanisms of vasculitis and support a mechanistic immunological classification. Especially, cytokine antagonism is pointing towards immunological distinctions between eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis/microscopic polyangiitis and differences between giant cell arteritis and Takayasu arteritis.
Topics: Churg-Strauss Syndrome; Etanercept; Giant Cell Arteritis; Granulomatosis with Polyangiitis; Humans; Microscopic Polyangiitis; Randomized Controlled Trials as Topic; Rituximab; Takayasu Arteritis
PubMed: 33872767
DOI: 10.1016/j.autrev.2021.102829 -
BMJ Open Ophthalmology Jun 2023This study aimed to review effectiveness studies comparing two biological anti-tumour necrosis factor agents, adalimumab (ADA) and infliximab (IFX), in the management of...
OBJECTIVE
This study aimed to review effectiveness studies comparing two biological anti-tumour necrosis factor agents, adalimumab (ADA) and infliximab (IFX), in the management of autoimmune uveitis.
METHODS
A systematic search was conducted across PubMed, Scopus, Web of Science and Google Scholar from 2014 until February 2022. The search included the following keywords "Adalimumab", "Infliximab", "Autoimmune", "Anterior", "Intermediate", "Posterior", "Panuveitis", "Refractory" and "Uveitis". Primary studies comparing both ADA and IFX in a population of autoimmune uveitis patients were considered. Outcomes of interest were measures of response to treatment and incidence of adverse events.
RESULTS
The preliminary literature search generated 7156 references. Six studies fulfilled the eligibility criteria and were included in the final analysis; all were non-randomised, retrospective or observational. The included studies found similar effectiveness and side effect profiles for both ADA and IFX in the management of autoimmune uveitis, however, one did not report effectiveness for each separately, and three were limited to Behcet's disease.
CONCLUSION
ADA and IFX seem to display comparable effectiveness and safety profiles. However, the available evidence remains scarce, of low quality and at high risk of bias. A direct comparison between ADA and IFX through large randomised controlled trials is needed to provide more substantial evidence of equivalence or superiority in uveitis.
Topics: Humans; Adalimumab; Infliximab; Retrospective Studies; Treatment Outcome; Uveitis; Tumor Necrosis Factor-alpha; Behcet Syndrome
PubMed: 37493653
DOI: 10.1136/bmjophth-2023-001303 -
International Journal of Clinical... Apr 2023Only one head-to-head comparison of advanced treatments in moderately to severely active ulcerative colitis (UC) has been published; therefore, there remains a need for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Only one head-to-head comparison of advanced treatments in moderately to severely active ulcerative colitis (UC) has been published; therefore, there remains a need for further comparisons.
AIM
The relative treatment effects of filgotinib and adalimumab, golimumab, infliximab, tofacitinib, ustekinumab and vedolizumab were estimated using a network meta-analysis (NMA).
METHOD
Systematically identified studies (MEDLINE, Embase and Cochrane Library; searched: inception-May 2019, updated November 2020) investigating treatments for moderately to severely active UC were re-evaluated for inclusion in a Bayesian NMA (fixed-effects model). Relative treatment effects were estimated using different permutations of patient population (biologic-naïve or biologic-experienced), treatment phase (induction or maintenance) and outcomes (MCS response/remission or endoscopic mucosal healing).
RESULTS
Seventeen trials (13 induction; 9 maintenance) were included in the NMA; 8 treatment networks were constructed. Most targeted therapies were superior to placebo in terms of MCS response/remission and endoscopic mucosal healing; filgotinib 200 mg was similar to most other treatments. Infliximab 5 mg/kg was superior to filgotinib 200 mg (biologic-naïve; induction) for MCS response/remission (mean relative effect, 0.34 [95% credible interval: 0.05, 0.62]). Filgotinib 200 mg was superior to adalimumab 160/80/40 mg for MCS response/remission (biologic-experienced; induction; - 0.75 [- 1.16, - 0.35]), and endoscopic mucosal healing (biologic-naïve; maintenance; - 0.90 [- 1.89, - 0.01]); and to golimumab 50 mg every 4 weeks (biologic-naïve; maintenance; - 0.46 [- 0.94, 0]) for MCS response/remission.
CONCLUSION
The current treatment landscape benefits patients with moderately to severely active UC, improving key outcomes; filgotinib 200 mg was similar to current standard of care in most outcomes.
Topics: Humans; Colitis, Ulcerative; Infliximab; Adalimumab; Network Meta-Analysis; Bayes Theorem; Biological Products
PubMed: 36484968
DOI: 10.1007/s11096-022-01509-1 -
Gastroenterology Feb 2022Starting biologic treatment early in the course of inflammatory bowel disease (IBD) may be associated with higher efficacy, especially in Crohn's disease (CD). (Meta-Analysis)
Meta-Analysis
Efficacy of Biologic Drugs in Short-Duration Versus Long-Duration Inflammatory Bowel Disease: A Systematic Review and an Individual-Patient Data Meta-Analysis of Randomized Controlled Trials.
BACKGROUND AND AIMS
Starting biologic treatment early in the course of inflammatory bowel disease (IBD) may be associated with higher efficacy, especially in Crohn's disease (CD).
METHODS
This was a systematic review and individual-patient data meta-analysis of all placebo-controlled trials of biologics approved for IBD at study inception (October 2015), using Vivli data-sharing platform. The primary outcome was the proportional biologic/placebo treatment effect on induction of remission in patients with short-duration (≤18 months) vs long-duration disease (>18 months) analyzed separately for CD and ulcerative colitis (UC). We used meta-regression to examine the impact of patients' characteristics on the primary outcome.
RESULTS
We included 25 trials, testing infliximab, adalimumab, certolizumab, golimumab, natalizumab, or vedolizumab (6168 patients with CD and 3227 patients with UC). In CD, remission induction rates were higher in pooled placebo and patients in active arms with short-duration disease of ≤18 months (41.4% [244 of 589]) compared with disease duration of >18 months (29.8% [852 of 2857], meta-analytically estimated odds ratio, 1.33; 95% confidence interval, 1.09-1.64). The primary outcome, proportional biologic/placebo treatment effect on induction of remission, was not different in short-duration disease of ≤18 months (n = 589, odds ratio, 1.47; 95% confidence interval, 1.01-2.15) compared with longer disease duration (n = 2857, odds ratio, 1.43; 95% confidence interval, 1.19-1.72). In UC trials, both the proportional biologic/placebo remission-induction effect and the pooled biologic-placebo effect were stable, regardless of disease duration. Primary outcome results remained unchanged when tested using alternative temporal cutoffs and when modeled for individual patient's covariates, including prior anti-tumor necrosis factor exposure.
CONCLUSIONS
There are higher rates of induction of remission with biologics and with placebo in early CD, resulting in a treatment to placebo effect ratio that is similar across disease durations. No such relationships between disease duration and outcomes was found in UC. PROSPERO registration: CRD42018041961.
Topics: Adalimumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biological Products; Certolizumab Pegol; Colitis, Ulcerative; Crohn Disease; Gastrointestinal Agents; Humans; Immunologic Factors; Infliximab; Natalizumab; Randomized Controlled Trials as Topic; Tumor Necrosis Factor Inhibitors
PubMed: 34757139
DOI: 10.1053/j.gastro.2021.10.037