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Inflammatory Bowel Diseases Apr 2024Patients undergoing organ transplantation are often on immunosuppressing medications to prevent rejection of the transplant. The data on use of concomitant... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients undergoing organ transplantation are often on immunosuppressing medications to prevent rejection of the transplant. The data on use of concomitant immunosuppression for inflammatory bowel disease (IBD) and organ transplant management are limited. This study sought to evaluate the safety of biologic and small molecule therapy for the treatment of IBD among solid organ transplant recipients.
METHODS
Medline, Embase, and Web of Science databases were systematically searched for studies reporting on safety outcomes associated with the use of biologic and small molecule therapy (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) in patients with IBD postsolid organ transplant (eg, liver, kidney, heart, lung, pancreas). The primary outcome was infectious complications. Secondary outcomes included serious infections, colectomy, and discontinuation of biologic therapy.
RESULTS
Seven hundred ninety-seven articles were identified for screening, yielding 16 articles for the meta-analyses with information on 163 patients. Antitumor necrosis factor α (Anti-TNFs; infliximab and adalimumab) were used in 8 studies, vedolizumab in 6 studies, and a combination of ustekinumab or vedolizumab and anti-TNFs in 2 studies. Two studies reported outcomes after kidney and cardiac transplant respectively, whereas the rest of the studies included patients with liver transplants. The rates of all infections and serious infections were 20.09 per 100 person-years (100-PY; 95% CI, 12.23-32.99 per 100-PY, I2 = 54%) and 17.39 per 100-PY (95% CI, 11.73-25.78 per 100-PY, I2 = 21%), respectively. The rates of colectomy and biologic medication discontinuation were 12.62 per 100-PY (95% CI, 6.34-25.11 per 100-PY, I2 = 34%) and 19.68 per 100-PY (95% CI, 9.97-38.84 per 100-PY, I2 = 74%), respectively. No cases of venous thromboembolism or death attributable to biologic use were reported.
CONCLUSION
Biologic therapy is overall well tolerated in patients with solid organ transplant. Long-term studies are needed to better define the role of specific agents in this patient population.
Topics: Humans; Adalimumab; Biological Products; Inflammatory Bowel Diseases; Infliximab; Organ Transplantation; Ustekinumab
PubMed: 37300512
DOI: 10.1093/ibd/izad108 -
BMJ Open Ophthalmology Jan 2023To facilitate the integration of eye care into universal health coverage, the WHO is developing a Package of Eye Care Interventions (PECI). Development of the PECI... (Review)
Review
To facilitate the integration of eye care into universal health coverage, the WHO is developing a Package of Eye Care Interventions (PECI). Development of the PECI involves the identification of evidence-based interventions from relevant clinical practice guidelines (CPGs) for uveitis.A systematic review of CPGs published on uveitis between 2010 and March 2020 was conducted. CPGs passing title and abstract and full-text screening were evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool and data on recommended interventions extracted using a standard data extraction sheet.Of 56 CPGs identified as potentially relevant from the systematic literature search, 3 CPGs underwent data extraction following the screening stages and appraisal with the AGREE II tool. These CPGs covered screening for, monitoring and treating juvenile idiopathic arthritis (JIA)-associated uveitis, the use of adalimumab and dexamethasone in treating non-infectious uveitis, and a top-level summary of assessment, differential diagnosis and referral recommendations for uveitis, aimed at primary care practitioners. Many of the recommendations were based on expert opinion, though some incorporated clinical study and randomised controlled trial data.There is currently sparse coverage of the spectrum of disease caused by uveitis within CPGs. This may partially be due to the large number of conditions with diverse causes and clinical presentations covered by the umbrella term uveitis, which makes numerous sets of guidelines necessary. The limited pool of CPGs to select from has implications for clinicians seeking guidance on clinical care strategies for uveitis.
Topics: Humans; Uveitis; Adalimumab; Arthritis, Juvenile
PubMed: 37278434
DOI: 10.1136/bmjophth-2022-001091 -
JAMA Dermatology Jul 2023Biosimilars have the potential to reduce costs for the management of moderate-to-severe psoriasis compared with originators. However, the extrapolation of evidence...
IMPORTANCE
Biosimilars have the potential to reduce costs for the management of moderate-to-severe psoriasis compared with originators. However, the extrapolation of evidence enables the approval of a biosimilar for use in indications held by the originator without directly being studied in clinical trials. Thus, biosimilars can be approved for psoriasis based on extrapolated evidence from other diseases. The availability of evidence for the effectiveness and safety of biosimilars for the treatment of psoriasis is therefore unclear.
OBJECTIVE
To compare the efficacy/effectiveness and safety of biosimilars with originator biologics for the treatment of patients with psoriasis.
EVIDENCE REVIEW
MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, and The European Union Clinical Trials Register were searched in August 2022. Eligible studies were appraised using the Cochrane Risk of Bias 2 and ROBINS-I tools. All analyses were conducted from September 2022 to November 2022.
FINDINGS
Fourteen trials (10 adalimumab, 2 etanercept, 1 infliximab, and 1 ustekinumab) and 3 cohort studies (1 adalimumab, 1 etanercept, 1 infliximab and etanercept) were included. Twelve trials compared biosimilars with originators in originator-naive patients (starters), and 11 trials compared switching from originator to biosimilar (switchers) with continuous originator treatments. There was no clinically or statistically significant difference in rates of achieving 75% improvement in Psoriasis Area and Severity Index scores and risks of adverse events (AEs) at week 16 and week 52 between the comparators. Two cohort studies showed no difference in effectiveness and safety outcomes between originators and biosimilars, whereas 1 study reported more AEs in patients who switched to biosimilars of adalimumab at 12 months. Three trials showed low risk of bias, whereas 11 trials had moderate risk of bias. All cohort studies had moderate to high risk of bias.
CONCLUSIONS AND RELEVANCE
In this systematic review, there was no clinically or statistically significant difference in the efficacy and safety between biosimilars and originators for the treatment of patients with psoriasis. Most of the available evidence was based on randomized clinical trials, although high-quality real-world evidence was lacking. Future studies are needed to examine the long-term effectiveness and safety of biosimilars for the treatment of patients with psoriasis.
Topics: Humans; Etanercept; Biosimilar Pharmaceuticals; Infliximab; Adalimumab; Psoriasis
PubMed: 37256582
DOI: 10.1001/jamadermatol.2023.1338 -
Cureus Apr 2023This meta-analysis has been conducted to compare ustekinumab and adalimumab as induction or maintenance therapy in patients with moderate to severe Crohn's disease... (Review)
Review
Comparison of Effectiveness and Safety of Ustekinumab and Adalimumab As Induction or Maintenance Therapy in Patients With Moderate to Severe Crohn's Disease: A Systematic Review and Meta-Analysis.
This meta-analysis has been conducted to compare ustekinumab and adalimumab as induction or maintenance therapy in patients with moderate to severe Crohn's disease (CD). The current meta-analysis was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two investigators independently searched online databases including PubMed, Cumulated Index to Nursing and Allied Health Literature (CINAHL), and Cochrane Library for relevant articles published up to April 2023. The initial search terms were "ustekinumab," "adalimumab," and "Crohn's disease". Three studies (with a total of 612 patients) were included in the present meta-analysis. We did not find any significant difference in clinical remission (OR: 1.31, 95% CI: 0.68-2.52), clinical response (OR: 1.39, 95% CI: 0.39-4.91), endoscopic remission (OR: 1.56, 95% CI: 0.66-3.64), and steroid-free remission (OR: 0.98, 95% CI: 0.67-1.42) between patients who received ustekinumab and patients who received adalimumab. In conclusion, this meta-analysis provides valuable insights into the efficacy and safety of ustekinumab and adalimumab in the treatment of moderate to severe CD. Our findings indicate that both drugs have similar effectiveness in achieving clinical remission, clinical response, radiological remission and steroid-free remission.
PubMed: 37255887
DOI: 10.7759/cureus.38277 -
BMC Ophthalmology May 2023To compare the efficacy and safety of infliximab with that of adalimumab in the treatment of non-infectious uveitis (NIU). (Meta-Analysis)
Meta-Analysis
PURPOSE
To compare the efficacy and safety of infliximab with that of adalimumab in the treatment of non-infectious uveitis (NIU).
METHODS
We searched for relevant studies in the PubMed, Embase, ClinicalTrials.gov, Cochrane Library databases, Grey Matters, Grey Literature Report, OpenGrey, China National Knowledge Infrastructure (CNKI), and Wan Fang databases up to September 2022. The incidences of complete remission of inflammation, response to therapy, adverse events and corticosteroid-sparing effect were evaluated.
RESULTS
Eleven clinical trials covering 1459 NIU patients were included. Complete remission of inflammation after therapy was achieved in 161 (37.5%) patients in the infliximab group and 151 (39.6%) patients in the adalimumab group. These two groups were not significantly different (P = 0.37). Four studies reported response to anti-TNF therapy involving 449 patients, of whom 241/272 (88.6%) treated with infliximab and 153/177 (86.4%) treated with adalimumab achieved partial or complete remission of inflammation. No significant difference was observed between the two cohorts in terms of response to therapy (P = 0.86). There was no significant difference between infliximab and adalimumab with regard to corticosteroid-sparing effect (P = 0.58). The pooled effect size (P = 0.001) showed a statistically significant difference, with the incidence of adverse events being 17.91% for infliximab and 12.12% for adalimumab.
CONCLUSION
Our systematic review and meta-analysis of 11 studies suggests that infliximab and adalimumab have similar therapeutic efficacy and corticosteroid-sparing effect in patients with NIU. However, adalimumab has a marginal advantage over infliximab in terms of adverse events. Large-scale RCTs with a longer follow-up are required to further evaluate these two anti-TNF-α agents in patients with NIU.
Topics: Humans; Adalimumab; Infliximab; Antibodies, Monoclonal; Tumor Necrosis Factor Inhibitors; Antibodies, Monoclonal, Humanized; Tumor Necrosis Factor-alpha; Uveitis; Inflammation
PubMed: 37248486
DOI: 10.1186/s12886-023-02987-1 -
Pharmaceutics Apr 2023Treatment of hidradenitis suppurativa (HS) is difficult and current guidelines are based mainly on expert opinion and non-randomized controlled trials. Recently, there... (Review)
Review
Treatment of hidradenitis suppurativa (HS) is difficult and current guidelines are based mainly on expert opinion and non-randomized controlled trials. Recently, there have been some targeted therapies using uniform primary endpoints for outcome assessment. Recommendations can be provided on selecting biologics and targeted synthetic small molecules for refractory HS by comparing the efficacy and safety of these medications. Databases including ClinicalTrial.gov, Cochrane Library, and PubMed were searched. Randomized controlled trials (RCTs) for moderate-to-severe HS were eligible. We performed random-effect network meta-analysis and ranking probability. The primary outcome was Hidradenitis Suppurativa Clinical Response (HiSCR) at 12-16 weeks. Secondary outcome included Dermatology Life Quality Index (DLQI) 0/1, mean change of DLQI from baseline, and adverse effects. A total of 12 RCTs involving 2915 patients were identified. Adalimumab, bimekizumab, secukinumab 300 mg q4w and secukinumab 300 mg q2w showed superiority to placebo in HiSCR at weeks 12 to 16. In addition, there was no significant difference between bimekizumab and adalimumab as measured by HiSCR (RR = 1.00; 95% CI: 0.66-1.52) and DLQI 0/1 (RR = 2.40, 95% CI: 0.88-6.50). In terms of ranking probability for achieving HiSCR at 12-16 weeks, adalimumab ranked first, followed by bimekizumab, secukinumab 300 mg q4w, and secukinumab 300 mg q2w. All biologics and small molecules did not differ in the development of adverse effects compared to placebo. Adalimumab, bimekizumab, secukinumab 300 mg q4w and secukinumab 300 mg q2w represent four regimens that produce better outcomes than placebo without increased risk of adverse events. Adalimumab and bimekizumab exhibited best HiSCR and DLQI 0/1 between weeks 12-16.
PubMed: 37242593
DOI: 10.3390/pharmaceutics15051351 -
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 -
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 -
Current Medical Research and Opinion Jun 2023The treatment of moderate-to-severe plaque psoriasis has seen significant improvements in recent years with the advent of biologic drugs. The aim of this study was to...
OBJECTIVE
The treatment of moderate-to-severe plaque psoriasis has seen significant improvements in recent years with the advent of biologic drugs. The aim of this study was to assess the cost-effectiveness of anti-IL17 drugs and other biologic therapies used to treat moderate-to-severe plaque psoriasis in France and Germany over a one-year time horizon.
METHODS
We developed a cost per responder model for biologic drugs used in psoriasis treatment. The model included anti-IL17s (brodalumab, secukinumab, ixekizumab and bimekizumab), anti-TNFs (adalimumab, etanercept, certolizumab and infliximab), an anti-IL12/23 (ustekinumab), and anti-IL23s (risankizumab, guselkumab and tildrakizumab). Efficacy estimates were collected through a systematic literature review of network meta-analyses on long-term Psoriasis Area and Severity Index (PASI) measures. Dose recommendations and country-specific prices were used to calculate drug costs. Biosimilar drug prices were used when available as a substitute for the originator drugs.
RESULTS
After one year, brodalumab had the lowest cost per PASI100-responder in both France (€20,220) and Germany (€26,807) across all available biologic treatments. Among the anti-IL17s, brodalumab had a 23% lower cost per PASI100-responder vs. the nearest comparator in France (bimekizumab, €26,369), and 30% lower vs. nearest comparator in Germany (ixekizumab, €38,027). Brodalumab also had the lowest cost per PASI75- and PASI90-responder among the anti-IL17s in both France and Germany after one year. Adalimumab had the lowest cost per PASI100-responder among the anti-TNFs in both France (€23,418) and Germany (€38,264). Among the anti-IL-23s, risankizumab had the lowest cost per PASI100-responder in both France (€20,969) and Germany (€26,994).
CONCLUSION
Driven by its lower costs and high response rates, brodalumab was the most cost-effective treatment option for moderate-to-severe plaque psoriasis over a one-year time-horizon within the anti-IL17 class and when compared to all other biologics in France and Germany.
Topics: Humans; Adalimumab; Ustekinumab; Infliximab; Treatment Outcome; Psoriasis; Biological Products; Severity of Illness Index
PubMed: 37203343
DOI: 10.1080/03007995.2023.2214046 -
Annals of Gastroenterology 2023Crohn's disease is a relapsing disease that often requires operative management. Prevention of postoperative recurrence (POR) is critical to maintain remissions....
BACKGROUND
Crohn's disease is a relapsing disease that often requires operative management. Prevention of postoperative recurrence (POR) is critical to maintain remissions. Biologic agents have proven to be most successful in remission maintenance. We made a direct head-to-head comparison of the 2 anti-tumor necrosis factor agents, infliximab (IFX) and adalimumab (ADA), to compare endoscopic and clinical POR of Crohn's disease.
METHODS
We conducted a comprehensive literature search in 7 databases, including Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science Core Collection, KCI-Korean Journal Index, SciELO, and Global Index Medicus. Odds ratios (OR) were calculated with 95% confidence intervals (CI) and P-values (<0.05 considered significant). We evaluated the total rates of endoscopic recurrence, endoscopic recurrence at 1 year, and clinical recurrence rates of IFX and ADA in a direct head-to-head comparison.
RESULTS
The search strategy yielded a total of 393 articles. Three studies with a total of 268 participants were included. Our meta-analysis showed no statistically significant difference in total endoscopic recurrence rate between ADA and IFX (27.1% vs. 32.3%, OR 0.696, 95%CI 0.403-1.201; P=0.193; =0%). Nor was there any significant difference between the drugs in endoscopic recurrence rate at 1 year (OR 0.799, 95%CI 0.329-1.940; P=0.620) or clinical recurrence rate (OR 0.477, 95%CI 0.477-1.712; P=0.755).
CONCLUSIONS
ADA and IFX show comparable efficacy in preventing POR endoscopically and clinically. The clinical decision should be based on cost, side-effects, tolerability, and patient preferences. Additional studies, particularly randomized controlled trials, are needed to determine generalizability.
PubMed: 37144019
DOI: 10.20524/aog.2023.0786