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International Journal of Dermatology May 2017Pyoderma gangrenosum (PG) is a sterile neutrophilic disorder that rarely affects children. Clinical, epidemiological, and therapeutic data on pediatric PG is poor as... (Review)
Review
Pyoderma gangrenosum (PG) is a sterile neutrophilic disorder that rarely affects children. Clinical, epidemiological, and therapeutic data on pediatric PG is poor as there are many newly reported associated diseases and drugs. This paper aims to review all recent available data on pediatric PG. A systematic review of the literature was conducted using Embase, Medline, and Cochrane databases. A total of 132 articles were included in the review. The most commonly reported underlying diseases in pediatric PG are inflammatory bowel diseases followed by hematologic disorders, vasculitis, immune deficiencies and Pyogenic Arthritis, Pyoderma gangrenosum and Acne (PAPA) syndrome. More than half of the cases occur with no underlying disease. The most frequently reported clinical presentation is multiple disseminated ulcers. Treatment should be tailored according to the underlying etiology. It includes systemic steroids, corticosteroid sparing agents such as dapsone and cyclosporine, and TNF-alpha inhibitors such as adalimumab and infliximab. Response to treatment is high with cure rates reaching 90%. A high index of suspicion and a thorough workup are mandatory in the management of pediatric PG.
Topics: Acne Vulgaris; Adolescent; Arthritis, Infectious; Child; Child, Preschool; Hematologic Diseases; Humans; Immunologic Deficiency Syndromes; Infant; Infant, Newborn; Inflammatory Bowel Diseases; Pyoderma Gangrenosum; Vasculitis
PubMed: 28233293
DOI: 10.1111/ijd.13584 -
Medicine Jun 2021Adalimumab is used as a first-line biologic agent in the management of moderate-to-severe hidradenitis suppurativa (HS). The objective of the present study was to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adalimumab is used as a first-line biologic agent in the management of moderate-to-severe hidradenitis suppurativa (HS). The objective of the present study was to evaluate the efficacy and safety of adalimumab in patients with moderate-to-severe HS.
METHODS
We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. Pooled estimates, namely standardized mean difference (SMD) and relative risk (RR), were calculated using random-effect model with trial sequential analysis. Small study effects were examined using the Doi plot. Certainty of evidence (CoE) was assessed using "The Grading of Recommendations Assessment, Development, and Evaluation" approach, and number-needed-to-treat (NNT) was calculated.
RESULTS
Five randomized controlled trials, involving 1014 patients, were included. We performed subgroup analysis of adalimumab administered subcutaneously both weekly and every other week. Adalimumab administered weekly was associated with better clinical response achievement (RR 1.76, 95% confidence interval [95% CI] 1.35-2.29; trial sequential analysis TSA-adjusted CI 1.01-3.08; CoE: low; NNT = 5) and a significant improvement in modified Sartorius score (SMD = -0.45, 95% CI = -0.76 to -0.13; CoE: very low; NNT = 10) and dermatology life quality index (DLQI) (SMD -0.47, 95% CI -0.61 to -0.32; CoE: low; NNT = 10). Nevertheless, adalimumab administered every other week showed an improvement only in modified Sartorius score. The pooled RRs of adverse events in both groups revealed no statistical significance when compared with the placebo.
CONCLUSIONS
Adalimumab administered weekly resulted in not only better clinical responses than placebo but also significantly improved disease severity and quality of life of patients with moderate-to-severe HS. Our study provides supporting evidence to the current guidelines and aids decision-making in the application of adalimumab in HS management.
Topics: Adalimumab; Adult; Antibodies, Monoclonal, Humanized; Case-Control Studies; Hidradenitis Suppurativa; Humans; Injections, Subcutaneous; Middle Aged; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha
PubMed: 34087885
DOI: 10.1097/MD.0000000000026190 -
The Cochrane Database of Systematic... Apr 2020Inflammatory bowel disease (IBD) is an umbrella term used to describe a group of chronic, progressive inflammatory disorders of the digestive tract. Crohn's disease and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Inflammatory bowel disease (IBD) is an umbrella term used to describe a group of chronic, progressive inflammatory disorders of the digestive tract. Crohn's disease and ulcerative colitis are the two main types. Fatigue is a common, debilitating and burdensome symptom experienced by individuals with IBD. The subjective, complex nature of fatigue can often hamper its management. The efficacy and safety of pharmacological or non-pharmacological treatments for fatigue in IBD is not yet established through systematic review of studies.
OBJECTIVES
To assess the efficacy and safety of pharmacological and non-pharmacological interventions for managing fatigue in IBD compared to no treatment, placebo or active comparator.
SEARCH METHODS
A systematic search of the databases Embase, MEDLINE, Cochrane Library, CINAHL, PsycINFO was undertaken from inception to July 2018. A top-up search was run in October 2019. We also searched the Cochrane IBD Group Specialized Register, the Cochrane Central Register of Controlled Trials, ongoing trials and research registers, conference abstracts and reference lists for potentially eligible studies.
SELECTION CRITERIA
Randomised controlled trials of pharmacological and non-pharmacological interventions in children or adults with IBD, where fatigue was assessed as a primary or secondary outcome using a generic or disease-specific fatigue measure, a subscale of a larger quality of life scale or as a single-item measure, were included.
DATA COLLECTION AND ANALYSIS
Two authors independently screened search results and four authors extracted and assessed bias independently using the Cochrane 'Risk of bias' tool. The primary outcome was fatigue and the secondary outcomes included quality of life, adverse events (AEs), serious AEs and withdrawal due to AEs. Standard methodological procedures were used.
MAIN RESULTS
We included 14 studies (3741 participants): nine trials of pharmacological interventions and five trials of non-pharmacological interventions. Thirty ongoing studies were identified, and five studies are awaiting classification. Data on fatigue were available from nine trials (1344 participants). In only four trials was managing fatigue the primary intention of the intervention (electroacupuncture, physical activity advice, cognitive behavioural therapy and solution-focused therapy). Electroacupuncture Fatigue was measured with Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) (scores range from 0 to 52). The FACIT-F score at week eight was 8.00 points higher (better) in participants receiving electroacupuncture compared with no treatment (mean difference (MD) 8.00, 95% CI 6.45 to 9.55; 1 RCT; 27 participants; low-certainty evidence). Results at week 16 could not be calculated. FACIT-F scores were also higher with electroacupuncture compared to sham electroacupuncture at week eight (MD 5.10, 95% CI 3.49 to 6.71; 1 RCT; 30 participants; low-certainty evidence) but not at week 16 (MD 2.60, 95% CI 0.74 to 4.46; 1 RCT; 30 participants; low-certainty evidence). No adverse events were reported, except for one adverse event in the sham electroacupuncture group. Cognitive behavioural therapy (CBT) and solution-focused therapy Compared with a fatigue information leaflet, the effects of CBT on fatigue are very uncertain (Inflammatory Bowel Disease-Fatigue (IBD-F) section I: MD -2.16, 95% CI -6.13 to 1.81; IBD-F section II: MD -21.62, 95% CI -45.02 to 1.78; 1 RCT, 18 participants, very low-certainty evidence). The efficacy of solution-focused therapy on fatigue is also very uncertain, because standard summary data were not reported (1 RCT, 98 participants). Physical activity advice One 2 x 2 factorial trial (45 participants) found physical activity advice may reduce fatigue but the evidence is very uncertain. At week 12, compared to a control group receiving no physical activity advice plus omega 3 capsules, FACIT-F scores were higher (better) in the physical activity advice plus omega 3 group (FACIT-F MD 6.40, 95% CI -1.80 to 14.60, very low-certainty evidence) and the physical activity advice plus placebo group (FACIT-F MD 9.00, 95% CI 1.64 to 16.36, very low-certainty evidence). Adverse events were predominantly gastrointestinal and similar across physical activity groups, although more adverse events were reported in the no physical activity advice plus omega 3 group. Pharmacological interventions Compared with placebo, adalimumab 40 mg, administered every other week ('eow') (only for those known to respond to adalimumab induction therapy), may reduce fatigue in patients with moderately-to-severely active Crohn's disease, but the evidence is very uncertain (FACIT-F MD 4.30, 95% CI 1.75 to 6.85; very low-certainty evidence). The adalimumab 40 mg eow group was less likely to experience serious adverse events (OR 0.56, 95% CI 0.33 to 0.96; 521 participants; moderate-certainty evidence) and withdrawal due to adverse events (OR 0.48, 95%CI 0.26 to 0.87; 521 participants; moderate-certainty evidence). Ferric maltol may result in a slight increase in fatigue, with better SF-36 vitality scores reported in the placebo group compared to the treatment group following 12 weeks of treatment (MD -9.31, 95% CI -17.15 to -1.47; 118 participants; low-certainty evidence). There may be little or no difference in adverse events (OR 0.55, 95% CI 0.26 to 1.18; 120 participants; low-certainty evidence) AUTHORS' CONCLUSIONS: The effects of interventions for the management of fatigue in IBD are uncertain. No firm conclusions regarding the efficacy and safety of interventions can be drawn. Further high-quality studies, with a larger number of participants, are required to assess the potential benefits and harms of therapies. Future studies should assess interventions specifically designed for fatigue management, targeted at selected IBD populations, and measure fatigue as the primary outcome.
Topics: Adalimumab; Anti-Inflammatory Agents; Cognitive Behavioral Therapy; Electroacupuncture; Exercise; Fatigue; Fatty Acids, Omega-3; Ferric Compounds; Hematinics; Humans; Inflammatory Bowel Diseases; Psychotherapy, Brief; Pyrones; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 32297974
DOI: 10.1002/14651858.CD012005.pub2 -
ClinicoEconomics and Outcomes Research... 2023Currently approved biologic therapies for moderate-to-severe ulcerative colitis have well-established efficacy. However, many patients fail to respond or lose response,... (Review)
Review
BACKGROUND
Currently approved biologic therapies for moderate-to-severe ulcerative colitis have well-established efficacy. However, many patients fail to respond or lose response, leading to dose escalation or treatment switching.
OBJECTIVE
We sought to identify real-world evidence on dose escalation and treatment switching and associated clinical and economic outcomes among adults with ulcerative colitis treated with infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, or tofacitinib.
METHODS
We conducted a systematic search of Embase, MEDLINE (up to 26 August 2020), and conference proceedings (2017-2020) for studies in adults with ulcerative colitis to assess clinical response and remission, colectomy, adverse events, and economic outcomes related to dose escalation and treatment switching.
RESULTS
In 56 studies, dose escalation and treatment switching involving infliximab and/or adalimumab were most frequently investigated. Rates of clinical response after dose escalation were 20-95% (1.8-36 months), clinical remission rates were 10-94% (1.8-36 months), colectomy rates were 0-33% (12-38 months), and adverse event rates were 0-18%. Treatment switching rates in 21 studies were 4-70% over 3-62 months, with switch due to loss of response rates of 4-35% over 12-62 months (7 studies). Up to 35% of patients underwent colectomy 12-120 weeks after switching, and 13-38% experienced adverse events. Data relating to economic outcomes were limited to tumor necrosis factor inhibitors, but demonstrated increased direct costs associated with both dose escalation and treatment switching.
CONCLUSION
Dose escalation and treatment switching are common with existing therapies. However, clinical response and remission rates vary, and a proportion of patients fail to achieve optimal clinical and economic outcomes. This highlights the need for more efficacious and durable treatments for patients with moderate-to-severe ulcerative colitis.
PubMed: 36855750
DOI: 10.2147/CEOR.S391413 -
BioDrugs : Clinical Immunotherapeutics,... Jun 2016Evidence-based studies are increasingly being focused on evaluating the efficacy and safety of adalimumab (ADA) for moderately to severely active ulcerative colitis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Evidence-based studies are increasingly being focused on evaluating the efficacy and safety of adalimumab (ADA) for moderately to severely active ulcerative colitis (UC). However, the dosage pattern of ADA for UC management is still not clear.
OBJECTIVE
A meta-analysis was conducted to evaluate the efficacy and safety of different ADA dosage regimens for moderately to severely active UC.
METHODS
The Medline, EMBASE, ISI Web of Knowledge, and Cochrane databases were searched from their inception to January 2015. Randomized controlled trials (RCTs) comparing ADA with placebo were eligible for initial inclusion. The efficacy and side effects were evaluated for ADA 160/80 (ADA 160/80 mg at weeks 0/2 and then 40 mg at weeks 4 and 6), and ADA 80/40 (ADA 80/40 mg at weeks 0/2 and then 40 mg at weeks 4 and 6) induction therapy, with ADA 40 mg every other week (EOW) for maintenance therapy of 52 weeks. The pooled risk ratio (RR) and its 95 % confidence interval (CI) were calculated.
RESULTS
Three RCTs were included. All of the studies were considered to have a low risk of bias. ADA 160/80 was more effective than placebo for induction of clinical remission (RR 1.62, 95 % CI 1.15-2.29), clinical response (RR 1.37, 95 % CI 1.19-1.59), mucosal healing (RR 1.27, 95 % CI 1.08-1.50), and inflammatory bowel disease questionnaire (IBDQ) response (RR 1.22, 95 % CI 1.05-1.43) and did not increase adverse events (RR 1.10, 95 % CI 0.95-1.27). Compared with placebo, ADA 80/40 did not show significant differences for induction of clinical remission and clinical response and did not increase adverse events. ADA 40 mg EOW was superior to placebo in maintaining clinical remission (RR 2.38, 95 % CI 1.57-3.59), clinical response (RR 1.69, 95 % CI 1.29-2.21), mucosal healing (RR 1.69, 95 % CI 1.26-2.28), and IBDQ response (RR 1.73, 95 % CI 1.28-2.34). Compared with placebo, ADA 40 mg EOW increased adverse events (RR 1.28, 95 % CI 1.06-1.54).
CONCLUSION
ADA 160/80 was a safe and effective treatment for induction management of moderately to severely active UC, but the benefits of ADA 80/40 application were limited. ADA 40 mg EOW was effective for maintenance management of UC. Additional well designed RCTs are needed to confirm these results.
Topics: Adalimumab; Anti-Inflammatory Agents; Colitis, Ulcerative; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Randomized Controlled Trials as Topic
PubMed: 27120055
DOI: 10.1007/s40259-016-0173-6 -
European Review For Medical and... Jul 2023The use of biological drugs to treat ulcerative colitis (UC) represents a clear added value; nevertheless, many patients do not have a sustained response to these drugs.... (Meta-Analysis)
Meta-Analysis
The comparative efficacy and safety of biologics and small molecules for treating patients with ulcerative colitis in Portugal: a systematic literature review and network meta-analysis.
OBJECTIVE
The use of biological drugs to treat ulcerative colitis (UC) represents a clear added value; nevertheless, many patients do not have a sustained response to these drugs. Small molecules were recently approved for the treatment of UC in Portugal. This network meta-analysis aimed to compare the efficacy and safety of the different therapies, including biological and small molecules, in patients prior exposed to biological treatment.
MATERIALS AND METHODS
A systematic review of the literature was performed on January 6, 2022, identifying all the relevant reports about the efficacy and safety of biologics (adalimumab, golimumab, infliximab, vedolizumab, ustekinumab) and small molecules (upadacitinib, filgotinib, tofacitinib) in the treatment of UC in Portugal. Network meta-analysis (NMA) was conducted using Bayesian Markov Chain Monte Carlo simulations. Results were presented in median Odds Ratio and Surface Under the Cumulative RAnking (SUCRA) score for each treatment.
RESULTS
Treatment of UC is divided into two phases: induction and maintenance. Upadacitinib 45 mg was the most efficacious therapy in achieving clinical remission and response and endoscopic improvement in the induction phase. Concerning the maintenance phase, upadacitinib 30 mg performed better than ustekinumab formulations in clinical remission and response, and endoscopic improvement. Regarding safety, there were no significant differences between all the drugs included in the analysis.
CONCLUSIONS
This network meta-analysis showed that upadacitinib reflects better efficacy compared to the available treatments for bio-exposed patients with moderate to severe UC. The safety profile is comparable to the other drugs.
Topics: Humans; Colitis, Ulcerative; Ustekinumab; Network Meta-Analysis; Portugal; Bayes Theorem; Biological Factors; Biological Products
PubMed: 37522686
DOI: 10.26355/eurrev_202307_33145 -
Inflammatory Bowel Diseases Jul 2014The aim of this meta-analysis was to explore the magnitude of the association between pharmacokinetics of adalimumab and clinical response in patients with inflammatory... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The aim of this meta-analysis was to explore the magnitude of the association between pharmacokinetics of adalimumab and clinical response in patients with inflammatory bowel disease.
METHODS
A literature search was performed up to December 2013. MEDLINE, EMBASE, Cochrane, and meeting abstracts were reviewed. Studies were included if they analyzed the association of trough levels of adalimumab (TRA) or antibodies against adalimumab (AAA) with clinical response in adult or pediatric inflammatory bowel disease. A Mantel-Haenszel pooled risk estimate provided a measure of the association.
RESULTS
Fourteen studies enrolling 1941 patients with inflammatory bowel disease were included in the systematic review. Thirteen studies analyzed clinical outcomes according to TRA. In only 1 study, there was no correlation between high TRA and clinical response. Six of the 7 studies reported a negative correlation between AAA and clinical outcomes. Six studies enrolling 536 patients (Crohn's disease [CD] only) met the meta-analysis inclusion criteria. The pooled odds ratio (OR) for loss of clinical response to adalimumab in patients with CD (N = 4) with positive AAAs was 10.15 (95% confidence interval [CI]: 3.90-26.40, P < 0.0001). Patients with CD with TRA over a predefined cutoff were more likely to be in clinical remission with an OR of 2.6 (95% CI: 1.79-3.77, P < 0.0001). The association was stronger if the analysis was limited to the adult population (N = 3, OR: 7.05, 95% CI: 3.58-13.9, P < 0.0001).
CONCLUSIONS
The presence of AAA is associated with a higher risk of loss of clinical response to adalimumab, whereas high TRA is associated with greater clinical response rates in CD. More data are needed in ulcerative colitis.
Topics: Adalimumab; Adult; Age Factors; Antibodies, Monoclonal, Humanized; Child; Colitis, Ulcerative; Crohn Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Inflammatory Bowel Diseases; Male; Monitoring, Physiologic; Risk Assessment; Severity of Illness Index; Treatment Outcome
PubMed: 24831559
DOI: 10.1097/MIB.0000000000000037 -
Rheumatology International Jun 2010Adalimumab (ADA) is a monoclonal antibody. Published studies indicate that its use in patients with rheumatoid arthritis can be efficient in providing long-term... (Comparative Study)
Comparative Study Meta-Analysis Review
Adalimumab (ADA) is a monoclonal antibody. Published studies indicate that its use in patients with rheumatoid arthritis can be efficient in providing long-term benefits. The aim of this study is to evaluate the efficacy and safety of ADA for treating rheumatoid arthritis. A systematic review was performed to search for randomized clinical trials that compare subcutaneous doses of ADA 20 mg weekly or 40 mg every other week with placebo, with or without concomitant methotrexate. Only studies of moderate or high quality were included. A meta-analysis was conducted to assess the efficacy (based in changes of American College of Rheumatology ACR criteria) and the safety (based in serious adverse events, serious infections, malignancy and deaths) of ADA use. Withdrawals due to adverse events or lack of efficacy were also evaluated. Eight studies met the inclusion criteria, comprising 2,692 patients. In the efficacy meta-analysis, a greater number of ADA-treated patients relative to those in placebo group achieved ACR20, ACR50 and ACR70 values from 6 months to 2 years of treatment. For safety results, there were no statistically significant differences between the groups. Withdrawals due to adverse events were higher in ADA group relative to the placebo group, and withdrawals due to the lack of efficacy were higher in placebo group relative to the ADA-treated group. This meta-analysis shows a higher efficacy of ADA relative to placebo, but clinicians should be careful regarding adverse events in ADA-treated patients.
Topics: Adalimumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Outcome Assessment, Health Care; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 19707765
DOI: 10.1007/s00296-009-1111-4 -
The Cochrane Database of Systematic... Feb 2011Biologics are used for the treatment of rheumatoid arthritis and many other conditions. While the efficacy of biologics has been established, there is uncertainty... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Biologics are used for the treatment of rheumatoid arthritis and many other conditions. While the efficacy of biologics has been established, there is uncertainty regarding the adverse effects of this treatment. Since serious risks such as tuberculosis (TB) reactivation, serious infections, and lymphomas may be common to the biologics but occur in small numbers across the various indications, we planned to combine the results from biologics used in many conditions to obtain the much needed risk estimates.
OBJECTIVES
To compare the adverse effects of tumor necrosis factor blocker (etanercept, adalimumab, infliximab, golimumab, certolizumab), interleukin (IL)-1 antagonist (anakinra), IL-6 antagonist (tocilizumab), anti-CD28 (abatacept), and anti-B cell (rituximab) therapy in patients with any disease condition except human immunodeficiency disease (HIV/AIDS).
METHODS
Randomized controlled trials (RCTs), controlled clinical trials (CCTs) and open-label extension (OLE) studies that studied one of the nine biologics for use in any indication (with the exception of HIV/AIDS) and that reported our pre-specified adverse outcomes were considered for inclusion. We searched The Cochrane Library, MEDLINE, and EMBASE (to January 2010). Identifying search results and data extraction were performed independently and in duplicate. For the network meta-analysis, we performed mixed-effects logistic regression using an arm-based, random-effects model within an empirical Bayes framework.
MAIN RESULTS
We included 163 RCTs with 50,010 participants and 46 extension studies with 11,954 participants. The median duration of RCTs was six months and 13 months for OLEs. Data were limited for tuberculosis (TB) reactivation, lymphoma, and congestive heart failure. Adjusted for dose, biologics as a group were associated with a statistically significant higher rate of total adverse events (odds ratio (OR) 1.19, 95% CI 1.09 to 1.30; number needed to treat to harm (NNTH) = 30, 95% CI 21 to 60) and withdrawals due to adverse events (OR 1.32, 95% CI 1.06 to 1.64; NNTH = 37, 95% CI 19 to 190) and an increased risk of TB reactivation (OR 4.68, 95% CI 1.18 to 18.60; NNTH = 681, 95% CI 143 to 14706) compared to control.The rate of serious adverse events, serious infections, lymphoma, and congestive heart failure were not statistically significantly different between biologics and control treatment. Certolizumab pegol was associated with significantly higher risk of serious infections compared to control treatment (OR 3.51, 95% CI 1.59 to 7.79; NNTH = 17, 95% CI 7 to 68). Infliximab was associated with significantly higher risk of withdrawals due to adverse events compared to control (OR 2.04, 95% CI 1.43 to 2.91; NNTH = 12, 95% CI 8 to 28). Indirect comparisons revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events compared to most other biologics. Although the overall numbers are relatively small, certolizumab pegol was associated with significantly higher odds of serious infections compared to etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab; abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections. Abatacept, adalimumab, etanercept and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events.
AUTHORS' CONCLUSIONS
Overall, in the short term biologics were associated with significantly higher rates of total adverse events, withdrawals due to adverse events and TB reactivation. Some biologics had a statistically higher association with certain adverse outcomes compared to control, but there was no consistency across the outcomes so caution is needed in interpreting these results.There is an urgent need for more research regarding the long-term safety of biologics and the comparative safety of different biologics. National and international registries and other types of large databases are relevant sources for providing complementary evidence regarding the short- and longer-term safety of biologics.
Topics: Antibodies, Monoclonal; Biological Products; Humans; Immunologic Factors; Patient Dropouts; Randomized Controlled Trials as Topic
PubMed: 21328309
DOI: 10.1002/14651858.CD008794.pub2 -
Frontiers in Pharmacology 2021Patients with noninfectious uveitis (NIU) are at risk of systemic side effects of long-term glucocorticoid therapy and uncontrolled inflammatory complications. In... (Review)
Review
Patients with noninfectious uveitis (NIU) are at risk of systemic side effects of long-term glucocorticoid therapy and uncontrolled inflammatory complications. In urgent need to identify more aggressive therapies, adalimumab (ADA) may be the right choice. To summarize the current evidence from randomized controlled trials (RCTs) regarding the efficacy and safety of ADA in the treatment of NIU. We searched Pubmed, Embase, Web of Science, Cochrane Library databases, and Clinical Trials Registry for qualifying articles from their inception to November 19, 2020, with no language restriction. Randomized controlled trials comparing ADA with conventional routine treatment in noninfectious uveitis patients of any age, gender, or ethnicity were included. The primary outcome was the time to treatment failure (TF). The secondary outcomes were the change in best-corrected visual acuity (BCVA), change in the anterior chamber (AC) cell grade, change in vitreous haze (VH) grade, and adverse events (AEs). The six studies comprised 605 participants in all, and the sample size of each study ranged from 16 to 225. The overall pooled results of the primary outcome (HR = 0.51; 95% CI, 0.41 to -0.63) showed that ADA nearly halved the risk of treatment failure compared to placebo for NIU patients. The pooled mean difference of change in BCVA was -0.05 (95% CI, -0.07 to -0.02). The pooled mean difference of change in AC cell grade and VH grade was -0.29 (95% CI, -0.62 to -0.05) and -0.21 (95% CI, -0.32 to -0.11), respectively. The incidence of AEs in the ADA group was numerically higher than that of AEs in the placebo group (2,237 events and 9.40 events per patient-year, equivalent to 1,257 events and 7.79 events per patient-year). This meta-analysis of six RCTs further confirmed that ADA considerably lowered the risk of treatment failure or visual loss, and moderately reduced AC cell grades and VH grades with slightly more AEs, as compared to placebo. ADA is both effective and safe in treating NIU. [https://clinicaltrials.gov], identifier [CRD42020217909].
PubMed: 33981245
DOI: 10.3389/fphar.2021.673984