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Digestive and Liver Disease : Official... Jun 2023The therapeutic armamentarium for the management of Crohn's disease (CD) is rapidly expanding. Several biologic therapies (e.g. infliximab, adalimumab, vedolizumab, and...
The therapeutic armamentarium for the management of Crohn's disease (CD) is rapidly expanding. Several biologic therapies (e.g. infliximab, adalimumab, vedolizumab, and ustekinumab) have been regulatory approved, and there is considerable practice variability in the treatment of patients with CD. This technical review systematically searched and identified the current evidence, synthesized it using meta-analytic methodology, appraised its quality, and concisely presented it, thus forming the basis for developing clinical practice recommendations on the use of biologic treatments in adult patients with CD.
Topics: Adult; Humans; Crohn Disease; Infliximab; Adalimumab; Ustekinumab; Biological Products
PubMed: 36964060
DOI: 10.1016/j.dld.2023.02.019 -
JAMA Dermatology May 2023Tumor necrosis factor-α inhibitors (TNFis) approved to treat several inflammatory diseases are sometimes used off label to treat severe forms of acne that are...
IMPORTANCE
Tumor necrosis factor-α inhibitors (TNFis) approved to treat several inflammatory diseases are sometimes used off label to treat severe forms of acne that are refractory to conventional therapies. However, use of TNFis can also be followed by acne occurrence, suggesting an association between TNFis and acne. Most of the literature on the topic comprises case reports and series that have not been reviewed in a systematic manner.
OBJECTIVE
To characterize the demographic characteristics, clinical presentations, treatments, and outcomes of patients receiving TNFis to treat acne and patients who develop acne following treatment of other conditions with TNFis.
EVIDENCE REVIEW
A systematic literature review was performed and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. PubMed and Web of Science were searched from inception through October 17, 2022. Included studies reported on patients of any sex or age who received TNFis whose treatment was followed by resolution or occurrence of acne. Two independent reviewers screened studies based on predefined criteria and extracted data from each study, which were quantitatively combined.
FINDINGS
A total of 53 studies reporting on 64 patients who received TNFis for the treatment of acne (n = 47) or who experienced acne after treatment with TNFis for a different condition (n = 17) (mean age, 28.7 years; range, 12-64 years; 6 female individuals [8.8%]) were included. The TNFis used included adalimumab, infliximab, and etanercept. Among the 47 patients treated for acne with TNFis, most had previously received antibiotics (31 [66.0%]) or isotretinoin (32 [68.1%]). Most (44 [93.6%]) experienced partial improvement (25 [53.2%]) or clearance (19 [40.4%]) with very few adverse effects reported (3 [6.4%]). Acne manifested as part of an inflammatory syndrome for 30 patients (63.8%). Among the 17 patients treated TNFis for a different condition followed by the occurrence of acne, only 1 patient (5.9%) reported having a history of acne. Therapy with TNFis was either discontinued (8 [47.1%]) or altered (6 [35.3%]) in most patients due to acne occurrence, typically with improvement in symptoms.
CONCLUSIONS AND RELEVANCE
The results of this systematic review suggest that TNFis can be effective in treating refractory acne but can also be associated with the occurrence of acne in certain instances. Further studies elucidating the role that TNF plays in treating and inducing acne could yield insight into off-label TNFi use and acne pathogenesis, potentially guiding clinical care of patients with acne treated or induced by TNFis.
Topics: Adult; Female; Humans; Acne Vulgaris; Adalimumab; Etanercept; Immunologic Factors; Infliximab; Tumor Necrosis Factor-alpha; Male; Child; Adolescent; Young Adult; Middle Aged
PubMed: 36930143
DOI: 10.1001/jamadermatol.2023.0269 -
Rheumatology and Therapy Apr 2023Biologic disease-modifying anti-rheumatic drugs (bDMARDs), including certolizumab pegol (CZP), are effective treatment options for the management of non-radiographic... (Review)
Review
Comparative Efficacy of Biologic Disease-Modifying Anti-Rheumatic Drugs for Non-Radiographic Axial Spondyloarthritis: A Systematic Literature Review and Bucher Indirect Comparisons.
INTRODUCTION
Biologic disease-modifying anti-rheumatic drugs (bDMARDs), including certolizumab pegol (CZP), are effective treatment options for the management of non-radiographic spondyloarthritis (nr-axSpA). In the absence of head-to-head comparisons in nr-axSpA, we conducted a systematic literature review (SLR) and indirect treatment comparison (ITC) to better understand the comparative efficacy of CZP vs. other bDMARDs.
METHODS
Literature searches were conducted in October 2020 in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials in patients with nr-axSpA who had failed at least one non-steroidal anti-inflammatory drug and were treated with bDMARDs. Outcomes of interest included the Assessment of Spondyloarthritis international Society (ASAS), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI) and Disease Activity Index (BASDAI), and spinal pain score. Comparative efficacy was examined using a series of Bucher ITCs in subgroups matched by prior exposure to bDMARDs, disease duration, baseline C-reactive protein (CRP) levels/magnetic resonance imaging (MRI) status, and timepoints, to ensure comparability between studies.
RESULTS
At 12-16 weeks, treatment with CZP was significantly more likely to achieve ASAS20/40 response and ASDAS-inactive disease status vs. etanercept (ETN), ixekizumab (IXE), and secukinumab (SEC). CZP showed statistically significant improvement in BASDAI, BASFI, and total spine pain score over adalimumab (ADA), ETN, and IXE, and in BASFI over SEC. Among patients with objective signs of inflammation (OSI; elevated CRP levels and/or inflammation on MRI at baseline), CZP had a statistically significant advantage over ETN and SEC (with or without loading dose) in achieving ASAS40, whereas the comparisons with other bDMARDs did not show any statistically significant differences.
CONCLUSION
In the overall matched population, CZP performed significantly better than most comparators in improving the clinical outcomes. Among patients with OSI, CZP was found to be superior to SEC (in the MRI-/CRP + and MRI + /CRP- subgroups) and ETN (in the MRI + /CRP- subgroup) and it was comparable to golimumab and IXE across the different OSI subgroups.
PubMed: 36633815
DOI: 10.1007/s40744-022-00522-0 -
Inflammatory Bowel Diseases Oct 2023Loss of response to infliximab or adalimumab in ulcerative colitis occurs frequently, and dose escalation may aid in regaining clinical benefit. This study aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Loss of response to infliximab or adalimumab in ulcerative colitis occurs frequently, and dose escalation may aid in regaining clinical benefit. This study aimed to systematically assess the annual loss of response and dose escalation rates for infliximab and adalimumab in ulcerative colitis.
METHODS
A systematic search was conducted from August 1999 to July 2021 for studies reporting loss of response and dose escalation during infliximab and/or adalimumab use in ulcerative colitis patients with primary response. Annual loss of response, dose escalation rates, and clinical benefit after dose escalation were calculated. Subgroup analyses were performed for studies with 1-year follow-up or less.
RESULTS
We included 50 unique studies assessing loss of response (infliximab, n = 24; adalimumab, n = 21) or dose escalation (infliximab, n = 21; adalimumab, n = 16). The pooled annual loss of response for infliximab was 10.1% (95% confidence interval [CI], 7.1-14.3) and 13.6% (95% CI, 9.3-19.9) for studies with 1-year follow-up. The pooled annual loss of response for adalimumab was 13.4% (95% CI, 8.2-21.8) and 23.3% (95% CI, 15.4-35.1) for studies with 1-year follow-up. Annual pooled dose escalation rates were 13.8% (95% CI, 8.7-21.7) for infliximab and 21.3% (95% CI, 14.4-31.3) for adalimumab, regaining clinical benefit in 72.4% and 52.3%, respectively.
CONCLUSIONS
Annual loss of response was 10% for infliximab and 13% for adalimumab, with higher rates during the first year. Annual dose escalation rates were 14% (infliximab) and 21% (adalimumab), with clinical benefit in 72% and 52%, respectively. Uniform definitions are needed to facilitate more robust evaluations.
Topics: Humans; Adalimumab; Colitis, Ulcerative; Infliximab; Retrospective Studies; Time Factors; Treatment Outcome
PubMed: 36318229
DOI: 10.1093/ibd/izac200 -
The Cochrane Database of Systematic... Jan 2020Psoriasis is an immune-mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Psoriasis is an immune-mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or joints, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. Several randomised controlled trials (RCTs) have compared the efficacy of the different systemic treatments in psoriasis against placebo. However, the relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis. This is the baseline update of a Cochrane Review first published in 2017, in preparation for this Cochrane Review becoming a living systematic review.
OBJECTIVES
To compare the efficacy and safety of conventional systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis, and to provide a ranking of these treatments according to their efficacy and safety.
SEARCH METHODS
We updated our research using the following databases to January 2019: the Cochrane Skin Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS and the conference proceedings of a number of dermatology meetings. We also searched five trials registers and the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) reports (until June 2019). We checked the reference lists of included and excluded studies for further references to relevant RCTs.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of systemic treatments in adults (over 18 years of age) with moderate-to-severe plaque psoriasis or psoriatic arthritis whose skin had been clinically diagnosed with moderate-to-severe psoriasis, at any stage of treatment, in comparison to placebo or another active agent. The primary outcomes of this review were: the proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90 at induction phase (from 8 to 24 weeks after the randomisation), and the proportion of participants with serious adverse effects (SAEs) at induction phase. We did not evaluate differences in specific adverse effects.
DATA COLLECTION AND ANALYSIS
Several groups of two review authors independently undertook study selection, data extraction, 'Risk of bias' assessment, and analyses. We synthesised the data using pair-wise and network meta-analysis (NMA) to compare the treatments of interest and rank them according to their effectiveness (as measured by the PASI 90 score) and acceptability (the inverse of serious adverse effects). We assessed the certainty of the body of evidence from the NMA for the two primary outcomes, according to GRADE, as either very low, low, moderate, or high. We contacted study authors when data were unclear or missing.
MAIN RESULTS
We included 140 studies (31 new studies for the update) in our review (51,749 randomised participants, 68% men, mainly recruited from hospitals). The overall average age was 45 years; the overall mean PASI score at baseline was 20 (range: 9.5 to 39). Most of these studies were placebo-controlled (59%), 30% were head-to-head studies, and 11% were multi-armed studies with both an active comparator and a placebo. We have assessed a total of 19 treatments. In all, 117 trials were multicentric (two to 231 centres). All but two of the outcomes included in this review were limited to the induction phase (assessment from 8 to 24 weeks after randomisation). We assessed many studies (57/140) as being at high risk of bias; 42 were at an unclear risk, and 41 at low risk. Most studies (107/140) declared funding by a pharmaceutical company, and 22 studies did not report the source of funding. Network meta-analysis at class level showed that all of the interventions (conventional systemic agents, small molecules, and biological treatments) were significantly more effective than placebo in terms of reaching PASI 90. At class level, in terms of reaching PASI 90, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents. At drug level, in terms of reaching PASI 90, infliximab, all of the anti-IL17 drugs (ixekizumab, secukinumab, bimekizumab and brodalumab) and the anti-IL23 drugs (risankizumab and guselkumab, but not tildrakizumab) were significantly more effective in reaching PASI 90 than ustekinumab and 3 anti-TNF alpha agents: adalimumab, certolizumab and etanercept. Adalimumab and ustekinumab were significantly more effective in reaching PASI 90 than certolizumab and etanercept. There was no significant difference between tofacitinib or apremilast and between two conventional drugs: ciclosporin and methotrexate. Network meta-analysis also showed that infliximab, ixekizumab, risankizumab, bimekizumab, guselkumab, secukinumab and brodalumab outperformed other drugs when compared to placebo in reaching PASI 90. The clinical effectiveness for these seven drugs was similar: infliximab (versus placebo): risk ratio (RR) 29.52, 95% confidence interval (CI) 19.94 to 43.70, Surface Under the Cumulative Ranking (SUCRA) = 88.5; moderate-certainty evidence; ixekizumab (versus placebo): RR 28.12, 95% CI 23.17 to 34.12, SUCRA = 88.3, moderate-certainty evidence; risankizumab (versus placebo): RR 27.67, 95% CI 22.86 to 33.49, SUCRA = 87.5, high-certainty evidence; bimekizumab (versus placebo): RR 58.64, 95% CI 3.72 to 923.86, SUCRA = 83.5, low-certainty evidence; guselkumab (versus placebo): RR 25.84, 95% CI 20.90 to 31.95; SUCRA = 81; moderate-certainty evidence; secukinumab (versus placebo): RR 23.97, 95% CI 20.03 to 28.70, SUCRA = 75.4; high-certainty evidence; and brodalumab (versus placebo): RR 21.96, 95% CI 18.17 to 26.53, SUCRA = 68.7; moderate-certainty evidence. Conservative interpretation is warranted for the results for bimekizumab (as well as tyrosine kinase 2 inhibitor, acitretin, ciclosporin, fumaric acid esters, and methotrexate), as these drugs, in the NMA, have been evaluated in few trials. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. Nevertheless, the SAE analyses were based on a very low number of events with low to very low certainty for just under half of the treatment estimates in total, and moderate for the others. Thus, the results have to be viewed with caution and we cannot be sure of the ranking. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1) the results were very similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions.
AUTHORS' CONCLUSIONS
Our review shows that compared to placebo, the biologics infliximab, ixekizumab, risankizumab, bimekizumab, guselkumab, secukinumab and brodalumab were the best choices for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of moderate- to high-certainty evidence (low-certainty evidence for bimekizumab). This NMA evidence is limited to induction therapy (outcomes were measured from 8 to 24 weeks after randomisation) and is not sufficient for evaluation of longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean age of 45 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice. Another major concern is that short-term trials provide scanty and sometimes poorly-reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. Indeed, we found no significant difference in the assessed interventions and placebo in terms of SAEs, but the evidence for all the interventions was of very low to moderate quality. In order to provide long-term information on the safety of the treatments included in this review, it will also be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies. In terms of future research, randomised trials comparing directly active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between conventional systemic and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve participants, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Chronic Disease; Cytokines; Humans; Immunosuppressive Agents; Molecular Targeted Therapy; Network Meta-Analysis; Psoriasis; Randomized Controlled Trials as Topic; Remission Induction; Severity of Illness Index; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 31917873
DOI: 10.1002/14651858.CD011535.pub3 -
Pediatric Rheumatology Online Journal Mar 2021Biologic disease modifying antirheumatic drugs (bDMARDs) and Janus Kinase (JAK) inhibitors are prescribed in adult and paediatric rheumatology. Due to age-dependent...
Biologic disease modifying antirheumatic drugs and Janus kinase inhibitors in paediatric rheumatology - what we know and what we do not know from randomized controlled trials.
BACKGROUND
Biologic disease modifying antirheumatic drugs (bDMARDs) and Janus Kinase (JAK) inhibitors are prescribed in adult and paediatric rheumatology. Due to age-dependent changes, disease course, and pharmacokinetic processes paediatric patients with inflammatory rheumatic diseases (PiRD) differ from adult rheumatology patients.
METHODS
A systematic literature search for randomized clinical trials (RCTs) in PiRD treated with bDMARDs/JAK inhibitors was conducted on Medline, clinicaltrials.gov , clinicaltrialsregister.eu and conference abstracts as of July 2020. RCTs were included if (i) patients were aged ≤20 years, (ii) patients had a predefined rheumatic diagnosis and (iii) RCT reported predefined outcomes. Selected studies were excluded in case of (i) observational or single arm study or (ii) sample size ≤5 patients. Study characteristics were extracted.
RESULTS
Out of 608 screened references, 65 references were selected, reporting 35 unique RCTs. All 35 RCTs reported efficacy while 34/3 provided safety outcomes and 16/35 provided pharmacokinetic data. The most common investigated treatments were TNF inhibitors (60%), IL-1 inhibitors (17%) and IL-6 inhibitors (9%). No RCTs with published results were identified for baricitinib, brodalumab, certolizumab pegol, guselkumab, risankizumab, rituximab, sarilumab, secukinumab, tildrakizumab, or upadacitinib. In patients with juvenile idiopathic arthritis (JIA) 25/35 RCTs were conducted. The remaining 10 RCTs were performed in non-JIA patients including plaque psoriasis, Kawasaki Disease, systemic lupus erythematosus and non-infectious uveitis. In JIA-RCTs, the control arm was mainly placebo and the concomitant treatments were either methotrexate, non-steroidal anti-inflammatory drugs (NSAID) or corticosteroids. Non-JIA patients mostly received NSAID. There are ongoing trials investigating abatacept, adalimumab, baricitinib, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, risankizumab, secukinumab, tofacitinib and tildrakizumab.
CONCLUSION
Despite the FDA Modernization Act and support of major paediatric rheumatology networks, such as the Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organization (PRINTO), which resulted in drug approval for PiRD indications, there are limited RCTs in PiRD patients. As therapy response is influenced by age-dependent changes, pharmacokinetic processes and disease course it is important to consider developmental changes in bDMARDs/JAK inhibitor use in PiRD patients. As such it is critical to collaborate and conduct international RCTs to appropriately investigate and characterize efficacy, safety and pharmacokinetics of bDMARDs/JAK inhibitors in paediatric rheumatology.
Topics: Antirheumatic Agents; Child; Humans; Janus Kinase Inhibitors; Randomized Controlled Trials as Topic; Rheumatic Diseases
PubMed: 33766063
DOI: 10.1186/s12969-021-00514-4 -
Dermatology Online Journal Dec 2020Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that can cause significant physical, mental, and socioeconomic burden. There remains a paucity of...
Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that can cause significant physical, mental, and socioeconomic burden. There remains a paucity of literature on HS in the pediatric population. This systematic review highlights recent advances in pediatric HS in epidemiology, presentation, comorbidities, and management. PubMed, Embase, Google Scholar, and Clinicaltrials.gov databases were used to identify trials and articles published on HS in pediatric patients between January 2015 and October 2019. A total of 39 articles were included. Current evidence suggests that pediatric onset HS may be associated with genetic factors along with endocrine and metabolic abnormalities. Delayed diagnosis in children with HS contributes to poor outcomes. Overall, children and adults with HS share similar lesion types and involved areas. Pediatric HS is associated with a number of comorbid conditions including acne, obesity, inflammatory joint disease, Down syndrome, inflammatory bowel disease, and diabetes. There are currently no pediatric treatment guidelines. Adalimumab is approved for the treatment of moderate-to-severe HS in children 12 and older. Other targeted immunomodulators and hormonal modulators are under investigation. Although the number of studies concerning HS are increasing, further investigation is warranted to better characterize HS, facilitate early diagnosis, and determine the best management for children.
Topics: 5-alpha Reductase Inhibitors; Antibodies, Monoclonal; Child; Finasteride; Hidradenitis Suppurativa; Humans; Tumor Necrosis Factor-alpha
PubMed: 33423411
DOI: No ID Found -
European Review For Medical and... Mar 2022For over ten years, adalimumab (ADA) has been approved for treating active moderate to severe Crohn's disease (CD), showing irreplaceable efficacy. However, the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
For over ten years, adalimumab (ADA) has been approved for treating active moderate to severe Crohn's disease (CD), showing irreplaceable efficacy. However, the difference in efficacy and prognosis when the disease pathology occurs in different locations of the body is still unclear. This study used systematic meta-analysis to assess the efficacy of ADA and prognosis in CD in different locations of disease pathology.
MATERIALS AND METHODS
We used "Adalimumab OR ADA OR HUMIRA OR IgG1 monoclonal antibody" AND "Crohn disease OR Crohn's disease OR CD OR IBD OR inflammatory bowel disease" as search strategies for searching electronic databases in the Embase, PubMed and CNKI databases. A systematic meta-analysis of proportions was performed to analyze the data.
RESULTS
A total of 1,253 patients in 15 articles were included in our study. The results showed that treatment with ADA led to overall remission rates that were elevated (70%, 95% CI: 58%-79%) but a nonnegligible overall relapse rate (28%, 95% CI: 12%-53%) in patients with CD. More importantly, we indicated that the use of ADA in patients with colon only (L2), ileum and colon (L3) and upper gastrointestinal tract (L4) CD led to significantly lower clinical remission rates. The use of ADA in patients with L2 led to significantly higher relapse rates, but the use of ADA in patients with ileum only (L1) and L3 CD led to significantly lower relapse rates.
CONCLUSIONS
Our findings clarify different remission and relapse rates depending on the location of the disease pathology and may be useful for clinicians' choice of treatment strategies.
Topics: Adalimumab; Antibodies, Monoclonal; Crohn Disease; Humans; Inflammatory Bowel Diseases; Prognosis; Remission Induction
PubMed: 35363354
DOI: 10.26355/eurrev_202203_28352 -
Medicine May 2024The goal of this study was to estimate the relative efficacy and safety of different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab,... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
The goal of this study was to estimate the relative efficacy and safety of different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) compared with placebo for systemic juvenile idiopathic arthritis (JIA) patients, through a network meta-analysis.
METHODS
Pubmed, Embase, and Cochrane Library were searched from database inception to July 2023 for randomized controlled trials comparing different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) or placebo directly or indirectly in JIA. Bayesian network meta-analyses were conducted. Data was extracted and analyzed by R with gemtc package. The treatment options were ranked using the surface under the cumulative ranking curve (SUCRA) value.
RESULTS
We identified 10 randomized controlled trials and analyzed 898 participants. Canakinumab (odds ratio 55.0, 95% credible intervals 2.4-67.0) was more effective than the placebo, and the difference was statistically significant. However, there was no statistical significance between other drugs versus placebo in terms of the modified ACRpedi30 (P > .05). The SUCRA shows that canakinumab ranked first (SUCRA, 86.9%), anakinra ranked second (SUCRA, 77.7%), adalimumab ranked third (SUCRA, 61.9%), and placebo ranked the last (SUCRA, 6.3%). Nevertheless, there were no notable discrepancies in the occurrence of adverse events, hepatic-related adverse events, infectious adverse event, serious adverse events, and serious infection following treatment with canakinumab, anakinra, tocilizumab, rilonacept, or the placebo. Based on the clustergram of modified ACRpedi30 and adverse events, canakinumab is suggested for JIA according to the surface under SUCRAs considering the symptom and adverse events simultaneously.
CONCLUSIONS
Among patients with JIA, canakinumab exhibited the highest likelihood of being the optimal treatment for achieving the modified ACRpedi30 response rate, and neither of the tested biological agents carried a significant risk of serious adverse events.
Topics: Arthritis, Juvenile; Humans; Network Meta-Analysis; Antirheumatic Agents; Randomized Controlled Trials as Topic; Treatment Outcome; Adalimumab; Antibodies, Monoclonal, Humanized; Interleukin 1 Receptor Antagonist Protein; Bayes Theorem
PubMed: 38701278
DOI: 10.1097/MD.0000000000038002 -
Frontiers in Medicine 2020Drug survival studies have been utilized to evaluate the real-world effectiveness of biologics used in psoriasis. However, the increasing volume of drug survival data...
Drug survival studies have been utilized to evaluate the real-world effectiveness of biologics used in psoriasis. However, the increasing volume of drug survival data suffers from large variability due to regional differences in drug availability, patient selection and biologic reimbursement. The objective of this study was to conduct a meta-analysis of biologic drug survival to determine comparative effectiveness of the biologics in a real-world setting. Studies reporting drug survival for biologic therapy in psoriasis were identified by a systematic literature search. Hazard ratio data for drug discontinuation were estimated directly from published Kaplan-Meier estimator curves at year 1, 2, and 5 of treatment and compared pairwise for the following biologics: ustekinumab, adalimumab, etanercept, infliximab, secukinumab, and ixekizumab. This pooled hazard ratios were used to estimate 2- and 5-year overall drug survival rates. Ustekinumab had the longest persistence at 2 and 5 years among all biologics included in this meta-analysis. Adalimumab was superior to etanercept and infliximab at 5 years. Pooled 5-year drug survival rates for adalimumab, etanercept, and infliximab were 46.3, 35.9, and 34.7%, respectively. Two- and five-year data were not available for anti-IL-17 drugs, but at 1-year ustekinumab outperformed secukinumab, the latter being equal to anti-TNFs. In conclusion, ustekinumab is characterized by longer drug survival than TNF inhibitors and IL-17 inhibitors. Estimated pooled 2- and 5-year drug survival rates may serve as a useful tool for patient communication and clinical decision-making.
PubMed: 33816514
DOI: 10.3389/fmed.2020.625755