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Rheumatology (Oxford, England) Sep 2020To assess the net benefit of biological agents (BA) used in JIA. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the net benefit of biological agents (BA) used in JIA.
METHODS
We systematically searched databases up to March 2019 for randomized controlled trials (RCT) performed in JIA disease. Separate random-effects meta-analyses were conducted for efficacy (ACR paediatric score 30%, ACRpedi30) and serious adverse events for safety. In order to standardize the baseline risk, we performed a meta-analysis of baseline risk in the control group (for both efficacy and safety meta-analysis). The net benefit was determined as the risk difference of efficacy subtracted by the risk difference of safety.
RESULTS
We included 19 trials: 11 parallel RCTs (754 patients) and 8 withdrawal RCTs (704 patients). The net benefit ranged from 2.4% (adalimumab) to 17.6% (etanercept), and from 2.4% (etanercept) to 36.7%, (abatacept) in parallel and withdrawal trials assessing non-systemic JIA, respectively. In the systemic JIA category, the net benefit ranged from 22.8% (rilonacept) to 70.3% (canakinumab), and from 32.3% (canakinumab) to 58.2% (tocilizumab) in parallel and withdrawal trials, respectively.
CONCLUSION
The results suggest that a greater number of patients experienced therapeutic success without serious adverse events in the systemic onset JIA category compared with the BAs for non-systemic JIA categories. Baseline risk, design of trial and JIA categories impact the measure of net benefit of BAs in JIA patients.
Topics: Abatacept; Adalimumab; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Juvenile; Biological Factors; Child; Etanercept; Female; Humans; Male; Randomized Controlled Trials as Topic; Regression Analysis; Risk Assessment; Treatment Outcome
PubMed: 32449926
DOI: 10.1093/rheumatology/keaa170 -
JAMA Dermatology Jul 2020Biologic therapies are widely prescribed immunomodulatory agents. There are concerns that compared with treatment with conventional systemic therapy, long-term biologic... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Biologic therapies are widely prescribed immunomodulatory agents. There are concerns that compared with treatment with conventional systemic therapy, long-term biologic treatment for common immune-mediated inflammatory diseases, namely inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and psoriasis, may be associated with increased risk of melanoma.
OBJECTIVE
To examine whether biologic treatment of IBD, RA, or psoriasis is associated with an increased risk of melanoma compared with conventional systemic therapy.
DATA SOURCES
Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles published from January 1, 1995, to February 7, 2019, for eligible studies.
STUDY SELECTION
Randomized clinical trials, cohort studies, and nested case-control studies quantifying the risk of melanoma in biologic-treated patients with IBD, RA, and psoriasis compared with patients treated with conventional systemic therapy were included.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted key study characteristics and outcomes. Study-specific risk estimates were pooled, and random- and fixed-effects model meta-analyses were conducted. Heterogeneity was assessed using the I2 statistic. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines were followed.
MAIN OUTCOMES AND MEASURES
The pooled relative risk (pRR) of melanoma in biologic-treated patients with IBD, RA, and psoriasis compared with biologic-naive patients treated with conventional systemic therapy.
RESULTS
Seven cohort studies comprising 34 029 biologic-treated patients and 135 370 biologic-naive patients treated with conventional systemic therapy were eligible for inclusion. Biologic treatment was positively associated with melanoma in patients with IBD (pRR, 1.20; 95% CI, 0.60-2.40), RA (pRR, 1.20; 95% CI, 0.83-1.74), or psoriasis (hazard ratio, 1.57; 95% CI, 0.61-4.09) compared with those who received conventional systemic therapy, but the differences were not statistically significant. Adjustment for other risk factors was absent from most studies.
CONCLUSIONS AND RELEVANCE
The findings suggest that clinically important increases in melanoma risk in patients treated with biologic therapy for common inflammatory diseases cannot be ruled out based on current evidence. However, further studies with large patient numbers that adjust for key risk factors are needed to resolve the issue of long-term safety of biologic therapy.
Topics: Abatacept; Adalimumab; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Biological Products; Etanercept; Humans; Inflammatory Bowel Diseases; Infliximab; Melanoma; Psoriasis; Risk Factors; Rituximab; Skin Neoplasms; Tumor Necrosis Factor Inhibitors
PubMed: 32432649
DOI: 10.1001/jamadermatol.2020.1300 -
Annals of the Rheumatic Diseases Jun 2020To perform an update of a review of the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA).
Pharmacological treatment of psoriatic arthritis: a systematic literature research for the 2019 update of the EULAR recommendations for the management of psoriatic arthritis.
OBJECTIVE
To perform an update of a review of the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA).
METHODS
This is a systematic literature research of 2015-2018 publications on all DMARDs in patients with PsA, searching Medline, Embase and the Cochrane Library. Efficacy was assessed in randomised controlled trials. For safety, cohort studies, case-control studies and long-term extensions (LTEs) were analysed.
RESULTS
56 publications (efficacy: n=33; safety n=23) were analysed. The articles were on tumour necrosis factor (TNF) inhibitors (n=6; golimumab, etanercept and biosimilars), interleukin (IL)-17A inhibitors (n=10; ixekizumab, secukinumab), IL-23-p19 inhibitors (n=2; guselkumab, risankizumab), clazakizumab (IL-6 inhibitor), abatacept (CD80/86 inhibitor) and ABT-122 (anti-TNF/IL-17A), respectively. One study compared ustekinumab (IL-12/23i) with TNF inhibitor therapy in patients with entheseal disease. Three articles investigated DMARD tapering. Trials on targeted synthetic DMARDs investigated apremilast (phosphodiesterase-4 inhibitor) and Janus kinase inhibitors (JAKi; tofacitinib, filgotinib). Biosimilar comparison with bio-originator showed non-inferiority. Safety was evaluated in 13 LTEs, 9 cohort studies and 1 case-control study investigating malignancies, infections, infusion reactions, multiple sclerosis and major cardiovascular events, as well as efficacy and safety of vaccination. No new safety signals were identified; however, warnings on the risk of venous thromboembolic events including pulmonary embolism when using JAKi were issued by regulators based on other studies.
CONCLUSION
Many drugs in PsA are available and have demonstrated efficacy against placebo. Efficacy varies across PsA manifestations. Safety must also be taken into account. This review informed the development of the European League Against Rheumatism 2019 updated PsA management recommendations.
Topics: Antirheumatic Agents; Arthritis, Psoriatic; Biological Products; Humans; Interleukin-17; Interleukin-23 Subunit p19; Molecular Targeted Therapy; Synthetic Drugs; Tumor Necrosis Factor-alpha
PubMed: 32381564
DOI: 10.1136/annrheumdis-2020-217163 -
Expert Review of Clinical Pharmacology May 2020The management of Psoriatic arthritis (PsA) has evolved in the last decade with a significant increase in treatment options making the choice for clinicians difficult....
INTRODUCTION
The management of Psoriatic arthritis (PsA) has evolved in the last decade with a significant increase in treatment options making the choice for clinicians difficult. Thus, the different factors of good prognosis for each treatment are presented in this review.
AREAS COVERED
Current available treatment and assessment tools for the response of treatment are presented. A systematic review of the literature, on Pubmed, Medline and Cochrane databases and abstracts from the last three EULAR and ACR annual conferences was performed. Factors associated with a good response to csDMARDs, tsDMARDs and bDMARDs are presented.
EXPERT OPINION
Dactylitis and axial involvement are associated with a poor response to methotrexate. Leflunomide has shown better efficacy in the presence of established polyarticular involvement. TNF inhibitors are to be preferred in young men with an elevated CRP while obesity, high disease activity and long disease duration are factors associated with poor response. Apremilast and ustekinumab are more effective in mono and oligo articular disease. Abatacept is more effective in patients with high CRP, high disease activity and polyarticular involvement. Finally, there are no available data with the anti IL17 These factors are some arguments to help clinicians, but comparative study are needed to conclude.
Topics: Antirheumatic Agents; Arthritis, Psoriatic; C-Reactive Protein; Female; Humans; Male; Prognosis; Treatment Outcome; Tumor Necrosis Factor Inhibitors
PubMed: 32306777
DOI: 10.1080/17512433.2020.1758556 -
Clinical and Experimental Rheumatology 2020This systematic literature review (SLR) and network meta-analysis (NMA) was aimed at comparing the relative efficacy and safety of abatacept (ABA) with other currently... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This systematic literature review (SLR) and network meta-analysis (NMA) was aimed at comparing the relative efficacy and safety of abatacept (ABA) with other currently recommended therapies for patients with early RA.
METHODS
An SLR (January 1998 to June 2018) was conducted including MEDLINE®, Embase, and CENTRAL databases, and grey literature. Population was adults with active RA for ≤2 years treated with biologic DMARDs as monotherapy or in combination with conventional DMARDs. A Bayesian NMA was performed using randomised controlled trials (RCTs) and comparisons for ACR50, DAS28 remission, withdrawal due to adverse events and total withdrawal where reported.
RESULTS
Ninety publications pertaining to 69 studies (43 RCTs and 26 observational studies) were identified. Twenty-eight RCTs were eligible to be included in the NMA. ABA as monotherapy was similar to the combination of ABA+methotrexate (MTX) for ACR50 (RR: 0.82 [95% CI 0.51-1.35]), and DAS28 remission (RR: 0.69 [95% CI 0.37-1.3]), as well as for withdrawal due to AEs (RR: 2.35 [95% CI 0.69-7.38]) and all-cause withdrawal (RR: 1.73 [95% CI 0.905-3.35]). ABA as monotherapy and ABA+MTX were both comparable to all other therapies for the main efficacy and safety outcomes. Observational study data reported was congruous with the RCT analysis.
CONCLUSIONS
The results of this NMA show similar efficacy and safety between ABA (as monotherapy or in combination with MTX) and other biologics in early RA. Further comparison of different treatment options for early RA is warranted as growing research provides evidence for the application of new novel therapies for RA.
Topics: Abatacept; Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Drug Therapy, Combination; Humans; Methotrexate; Network Meta-Analysis
PubMed: 32301430
DOI: No ID Found -
Arthritis Care & Research Jun 2021In rheumatoid arthritis, the association between advanced therapies (including biologic disease-modifying antirheumatic drugs [DMARDs] and targeted synthetic DMARDs) and... (Meta-Analysis)
Meta-Analysis
Most Appropriate Conventional Disease-Modifying Antirheumatic Drug to Combine With Different Advanced Therapies in Rheumatoid Arthritis: A Systematic Literature Review With Meta-Analysis.
OBJECTIVE
In rheumatoid arthritis, the association between advanced therapies (including biologic disease-modifying antirheumatic drugs [DMARDs] and targeted synthetic DMARDs) and methotrexate (MTX) is recommended by international societies. When MTX cannot be used, other conventional synthetic DMARDs (csDMARDs) may be proposed. We aimed to compare the safety and efficacy of MTX and non-MTX csDMARDs in combination with advanced therapies.
METHODS
We systematically searched the literature for studies comparing the effectiveness, retention rate, and safety of MTX versus non-MTX csDMARDs (leflunomide or others) in combination with tumor necrosis factor inhibitors (TNFi), abatacept, rituximab, tocilizumab, and JAK inhibitors. Meta-analysis was performed with RevMan, using an inverse variance approach with fixed or random-effects models. Risk ratios (RRs) and 95% confidence intervals (95% CIs) were estimated.
RESULTS
The literature search revealed 3,842 articles; 41 studies were included for the systematic literature review and 21 for the meta-analysis: 13 with TNFi, 3 with abatacept, and 5 with rituximab. For TNFi, the European Alliance of Associations for Rheumatology (EULAR) response at 6 months was lower for patients receiving non-MTX csDMARDs than for those using MTX (RR 0.93 [95% CI 0.87, 1.0], P = 0.04; n = 3,843; I = 28%), with a lower retention rate at 12 months. For abatacept, effectiveness and safety were similar between the 2 groups. For rituximab, a good EULAR response was higher with leflunomide than MTX (RR 1.38 [95% CI 1.13, 1.68], P = 0.001; n = 2,078; I = 0%), with similar adverse event rates. Meta-analysis for tocilizumab or JAK inhibitors could not be performed.
CONCLUSION
The different csDMARDs seem safe and efficient to combine with advanced therapies in RA patients. Although MTX seems slightly superior to other csDMARDs in combination with TNFi, leflunomide might be superior to MTX in combination with rituximab.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Drug Therapy, Combination; Humans; Janus Kinase Inhibitors; Methotrexate; Molecular Targeted Therapy; Time Factors; Treatment Outcome; Tumor Necrosis Factor Inhibitors
PubMed: 32216091
DOI: 10.1002/acr.24195 -
RMD Open Feb 2020Biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs are used in patients with psoriatic arthritis (PsA), but few studies directly... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs are used in patients with psoriatic arthritis (PsA), but few studies directly compare their clinical efficacy. In such situations, network meta-analysis (NMA) can inform evidence-based decision-making.
OBJECTIVE
To evaluate the comparative efficacy and safety of approved bDMARDs in patients with PsA.
METHODS
Bayesian NMA was conducted to compare the clinical efficacy of bDMARDs at weeks 12‒16 in bDMARD-naïve patients with PsA in terms of American College of Rheumatology (ACR) criteria, Psoriatic Arthritis Response Criteria (PsARC) and Psoriasis Area and Severity Index (PASI). Safety end points were evaluated in the overall mixed population of bDMARD-naive and bDMARD-experienced patients.
RESULTS
For ACR, all treatments except abatacept were statistically superior to placebo. Infliximab was most effective, followed by golimumab and etanercept, which were statistically superior to most other treatments. Ixekizumab 80 mg every 2 weeks (Q2W) was statistically superior to abatacept subcutaneous, apremilast and both regimens of ustekinumab; similar findings were observed for ixekizumab 80 mg Q4W. For PsARC response, ixekizumab did not significantly differ from other therapies, except for golimumab, infliximab and etanercept, which were superior to most other agents including ixekizumab. For PASI response, infliximab was numerically most effective, but was not statistically superior to ixekizumab, which was the next best performing agent. Analysis of safety end points identified few differences between treatments.
CONCLUSION
Our NMA confirms the efficacy and acceptable safety profile of bDMARDs in patients with active PsA. There were generally few statistically significant differences between most treatments.
Topics: Abatacept; Adult; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Psoriatic; Biological Products; Clinical Decision-Making; Humans; Immune Checkpoint Inhibitors; Interleukin-17; Network Meta-Analysis; Placebos; Safety; Severity of Illness Index; Treatment Outcome
PubMed: 32094304
DOI: 10.1136/rmdopen-2019-001117 -
Annals of the Rheumatic Diseases Jun 2020To perform a systematic literature review (SLR) concerning the safety of synthetic (s) and biological (b) disease-modifying anti rheumatic dugs (DMARDs) to inform the...
Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis.
OBJECTIVES
To perform a systematic literature review (SLR) concerning the safety of synthetic (s) and biological (b) disease-modifying anti rheumatic dugs (DMARDs) to inform the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis (RA).
METHODS
An SLR of observational studies comparing safety outcomes of any DMARD with another intervention for the management of RA. A comparator group was required for inclusion. For treatments still without registry data (eg, sarilumab and the Janus kinase (JAK) inhibitors baricitinib, upadacitinib), randomised controlled trials (RCTs) and long-term extensions (LTEs) were used. Risk of bias (RoB) was assessed according to standard procedures.
RESULTS
Forty-two observational studies fulfilled the inclusion criteria, addressing safety outcomes with bDMARDs and sDMARDs. Nine studies showed no difference in the risk of serious infections across bDMARDs and two studies (high RoB) showed an increased risk with bDMARDs compared with conventional synthetic (cs) DMARDs (adjusted incidence rate ratio 3.1-3.9). The risk of Herpes zoster infection was similar across bDMARDs, but one study showed an increased risk with tofacitinib compared with abatacept (adjusted HR (aHR) 2.0). Five studies showed no increased risk of cancer for bDMARDs compared with csDMARDs. An increased risk of lower intestinal perforation was found for tocilizumab compared with csDMARDs (aHR 4.5) and tumour necrosis factor inhibitor (TNFi) (aHR 2.6-4.0). Sixty manuscripts reported safety data from RCTs/LTEs. Overall, no unexpected safety outcomes were found, except for the possibly increased risk of venous thromboembolism (VTE) with JAK inhibitors.
CONCLUSION
Data obtained by this SLR confirm the known safety profile of bDMARDs. The risk of VTE in RA, especially in patients on JAK inhibitors, needs further evaluation.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Cardiovascular Diseases; Herpes Zoster; Humans; Infections; Intestinal Perforation; Neoplasms; Observational Studies as Topic; Randomized Controlled Trials as Topic; Synthetic Drugs; Venous Thromboembolism
PubMed: 32033941
DOI: 10.1136/annrheumdis-2019-216653 -
Annals of the Rheumatic Diseases Jun 2020To inform the 2019 update of the European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA).
Efficacy of pharmacological treatment in rheumatoid arthritis: a systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis.
OBJECTIVES
To inform the 2019 update of the European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA).
METHODS
A systematic literature research (SLR) to investigate the efficacy of any disease-modifying antirheumatic drug (DMARD) (conventional synthetic (cs)DMARD, biological (b) and biosimilar DMARD, targeted synthetic (ts)DMARD) or glucocorticoid (GC) therapy in patients with RA was done by searching MEDLINE, Embase and the Cochrane Library for articles published between 2016 and 8 March 2019.
RESULTS
234 abstracts were selected for detailed assessment, with 136 finally included. They comprised the efficacy of bDMARDs versus placebo or other bDMARDs, efficacy of Janus kinase (JAK) inhibitors (JAKi) across different patient populations and head-to-head of different bDMARDs versus JAKi or other bDMARDs. Switching of bDMARDs to other bDMARDs or tsDMARDs, strategic trials and tapering studies of bDMARDs, csDMARDs and JAKi were assessed. The drugs evaluated included abatacept, adalimumab, ABT-122, baricitinib, certolizumab pegol, SBI-087, CNTO6785, decernotinib, etanercept, filgotinib, golimumab, GCs, GS-9876, guselkumab, hydroxychloroquine, infliximab, leflunomide, mavrilimumab, methotrexate, olokizumab, otilimab, peficitinib, rituximab, sarilumab, salazopyrine, secukinumab, sirukumab, tacrolimus, tocilizumab, tofacitinib, tregalizumab, upadacitinib, ustekinumab and vobarilizumab. The efficacy of many bDMARDs and tsDMARDs was shown. Switching to another tumour necrosis factor inhibitor (TNFi) or non-TNFi bDMARDs after TNFi treatment failure is efficacious. Tapering of DMARDs is possible in patients achieving long-standing stringent clinical remission; in patients with residual disease activity (including patients in LDA) the risk of flares is increased during the tapering. Biosimilars are non-inferior to their reference products.
CONCLUSION
This SLR informed the task force regarding the evidence base of various therapeutic regimen for the development of the update of EULAR's RA management recommendation.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Biosimilar Pharmaceuticals; Drug Substitution; Drug Therapy, Combination; Glucocorticoids; Humans; Janus Kinase Inhibitors; Randomized Controlled Trials as Topic; Synthetic Drugs; Tumor Necrosis Factor-alpha
PubMed: 32033937
DOI: 10.1136/annrheumdis-2019-216656 -
Clinical and Experimental Rheumatology 2020There is no hierarchy in the use of biotherapies (bDMARDs) in psoriatic arthritis (PsA) and no published head-to-head comparative studies. Our purpose is to evaluate the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
There is no hierarchy in the use of biotherapies (bDMARDs) in psoriatic arthritis (PsA) and no published head-to-head comparative studies. Our purpose is to evaluate the respective efficacy of TNF inhibitors, IL12/23 inhibitors (ustekinumab), IL17 inhibitors (secukinumab, ixekizumab) and CTLA4Ig (abatacept) on articular, enthesitis, dactylitis, skin and functional outcomes in PsA.
METHODS
Randomised controlled trials assessing bDMARDs in PsA were selected through the MedLine, Cochrane and Embase databases. ACR20/50/70 and PASI75/90 response rates, enthesitis and dactylitis reduction rates and HAQ-DI mean reductions were collected. Pooled meta-analyses were performed to assess relative risks (RR) with their 95% confidence interval (95%CI) for each class of bDMARDs in comparison with placebo.
RESULTS
17 RCTs were analysed. Compared to placebo, all bDMARDs showed higher ACR20 response rates, with RRs ranging from 1.77 (1.31, 2.39) to 3.21 (2.52, 4.08), and a greater HAQ-DI mean reduction. TNF inhibitors, secukinumab and IL17 inhibitors showed higher ACR50/70 and PASI75/90 response rates. TNF inhibitors, secukinumab and IL17 inhibitors showed higher enthesitis resolution rates and only TNF inhibitors and IL17 inhibitors showed higher dactylitis resolution rates, with RRs ranging from 1.41 (1.02, 1.95) to 2.31 (1.60, 3.34) and from 2.07 (1.38, 3.12) to 2.65 (1.79, 3.94), respectively.
CONCLUSIONS
All bDMARDs showed higher ACR20 response rates and better HAQ-DI mean reduction compared to placebo. This meta-analysis highlights the variability of bDMARD efficacy on ACR50/70, PASI75/90 and enthesitis or dactylitis response rates. Head-to-head studies are needed to draw definitive conclusions on potential efficacy-related differences between bDMARDs in PsA.
Topics: Abatacept; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Psoriatic; Enthesopathy; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Ustekinumab
PubMed: 31969228
DOI: No ID Found