-
Medicine Jun 2021To evaluate the efficacy of fusion proteins biologics (Etanercept (ETN), Anakinra (ANA), and Abatacept) combinations in the treatment of rheumatoid arthritis (RA) using... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To evaluate the efficacy of fusion proteins biologics (Etanercept (ETN), Anakinra (ANA), and Abatacept) combinations in the treatment of rheumatoid arthritis (RA) using network meta-analysis to rank those according to their performance medicines. The performance of these processes is ranked according to the results of the analysis and an explanatory study of the possible results is carried out.
METHODS
Multiple databases including PubMed, EMBASE, and Cochrane Library were used to identify applicable articles and collect relevant data to analyze using STATA (14.0) software. The literature included in this study was divided into a combination of a placebo, methotrexate (MTX), and an observation group (1 of the 3 drugs). The last search date was December 12, 2019.
RESULTS
A total of 19 eligible randomized controlled trials of fusion proteins biologics were identified, a total of 1109 papers were included, and the results showed that the ETN + MTX had the highest probability of being the most clinically efficacious intervention, with a surface under the cumulative ranking curve of 91.6, was significantly superior (P < .05). Patients who had received ETN or ETN + MTX or ANA had effective compared with patients who had received placebo (95% CI 1.28%-8.47%; 1.92%-19.18%; 1.06%-10.45%).
CONCLUSIONS
1. The combination of ETN and MTX had the highest probability of optimal treatment compared to other drugs and 2. ENT, ENT + MTX, and ANA were effective in the treatment of RA compared to placebo.
Topics: Abatacept; Antirheumatic Agents; Arthritis, Rheumatoid; Biological Factors; Drug Therapy, Combination; Etanercept; Humans; Interleukin 1 Receptor Antagonist Protein; Methotrexate; Network Meta-Analysis
PubMed: 34128886
DOI: 10.1097/MD.0000000000026350 -
Clinical and Experimental Rheumatology Jul 2023There is an increasing body of evidence suggesting a direct pathophysiological role of anti-citrullinated peptide antibodies (ACPA) in rheumatoid arthritis (RA), and...
Changes of anti-citrullinated peptide antibodies titers after biologic treatment in patients with rheumatoid arthritis: a systematic literature review and retrospective study.
OBJECTIVES
There is an increasing body of evidence suggesting a direct pathophysiological role of anti-citrullinated peptide antibodies (ACPA) in rheumatoid arthritis (RA), and immunological remission could be a target for treatment. However, data related to the ability of biologics to reduce ACPA titres are contradictory.We aimed to evaluate the changes in ACPA titres after treatment with different biologics in patients with RA.
METHODS
As a first step, a systematic review of the literature available on 3 biologics (TNFi, abatacept and rituximab) and ACPA in patients with RA was performed in Pubmed and Cochrane. As a second step, a retrospective study was performed: all RA patients treated with the 3 above-mentioned biologics were identified. To be included in the analysis, patients had to have at least two titres of ACPA (one before and one after biologic treatment) available. ACPA titres were compared before and after treatment in each of the treatment groups.
RESULTS
As a result of the literature review, 24 articles were retained confirming that the data on change in ACPA under biologics is contradictory, particularly for abatacept and TNFi. 144 RA patients (79.3% female, mean age: 56 years) were included in the retrospective analysis: 59 patients had received rituximab, 31 abatacept, 55 TNFi. ACPA titres decreased significantly with rituximab but not with abatacept nor TNFi. Modelling of ACPA titres over follow-up confirmed the significant decrease of ACPA over time rituximab.
CONCLUSIONS
In this real-life study, ACPA titres only significantly decreased after treatment with rituximab.
Topics: Humans; Female; Middle Aged; Male; Abatacept; Antirheumatic Agents; Retrospective Studies; Rituximab; Anti-Citrullinated Protein Antibodies; Arthritis, Rheumatoid; Biological Products
PubMed: 36533995
DOI: 10.55563/clinexprheumatol/1h6h71 -
BMC Rheumatology 2020Dose loading of biological disease modifying anti-rheumatic drugs (bDMARDs) in auto-immune rheumatic diseases (AIRDs) is performed to achieve steady state drug...
The pharmacological and clinical aspects behind dose loading of biological disease modifying anti-rheumatic drugs (bDMARDs) in auto-immune rheumatic diseases (AIRDs): rationale and systematic narrative review of clinical evidence.
BACKGROUND
Dose loading of biological disease modifying anti-rheumatic drugs (bDMARDs) in auto-immune rheumatic diseases (AIRDs) is performed to achieve steady state drug concentrations earlier after treatment start compared to dosing regimens without loading. Although loading inherently results in increased costs, treatment targets in terms of reduced disease activity may be achieved at an earlier state. It is an interesting topic that, surprisingly, has not received much attention in literature.
METHODS
In this review, we aimed at providing a theoretical description of the pharmacodynamic / -kinetic rationale for dose loading of bDMARDs in AIRDs and to systematically review the clinical evidence on the effectiveness of dose loading on disease activity in AIRDs.
RESULTS
Only a small number of studies ( = 5) has been published comparing the effectiveness of dose loading versus a regimen without dose loading of bDMARDs in AIRDs, addressing abatacept ( = 2), certolizumab pegol ( = 1), and secukinumab (n = 2). These studies provide insufficient evidence on superiority of dose loading in terms of disease activity compared to a dosing regimen without loading, while safety issues might be comparable.
CONCLUSIONS
Although dose loading is commonly adopted for several bDMARDs in AIRDs, scientific evidence on its effectiveness and safety is surprisingly scarce and does not suggest superiority compared to a regimen without dose loading. More research in this field, also with regard to the pharmaco-economic consequences of dose loading, is urgently needed.
PubMed: 32743343
DOI: 10.1186/s41927-020-00130-x -
Clinical and Experimental Rheumatology 2020The objective of this study was to investigate whether anti-cyclic citrullinated peptide antibody (ACPA) status is associated with clinical responses to abatacept or... (Meta-Analysis)
Meta-Analysis
Presence of anti-cyclic citrullinated peptide antibodies is associated with better treatment response to abatacept but not to TNF inhibitors in patients with rheumatoid arthritis: a meta-analysis.
OBJECTIVES
The objective of this study was to investigate whether anti-cyclic citrullinated peptide antibody (ACPA) status is associated with clinical responses to abatacept or TNF-α-inhibitors (TNF-α-i) in RA patients.
METHODS
A systematic literature review (SLR) was performed in January 2018 to identify published studies and conference abstracts evaluating biologic DMARD response according to ACPA status. Mantel-Haenszel meta-analysis methods were used to pool risk ratios (RRs). In the base-case, treatment response was assessed using EULAR measure, while a scenario analysis assessed response by combining ACR20, DAS28 and EULAR measures. Subgroup analyses were performed for duration of study follow-up.
RESULTS
Eighteen of the 30 SLR studies were included in the meta-analysis. The base-case showed a statistically significant positive association between ACPA positivity and EULAR response for patients treated with abatacept (RR: 1.13 [95% CI: 1.00, 1.26]), while ACPA positivity was associated with lower EULAR responses to TNF-α-i (RR: 0.91 [95% CI: 0.84, 0.98]). For the scenario analysis, results were consistent with the base-case for abatacept (RR 1.18 [95% CI 1.03, 1.35]), while for TNFα-i, no significant difference by ACPA status was observed (RR 0.97 [95% CI 0.86, 1.10]). Subgroups analyses showed results similar to the base-case for both abatacept and TNF-α-i.
CONCLUSIONS
This meta-analysis confirms that ACPA-positive RA patients are marginally more likely to achieve EULAR and ACR20 response to abatacept compared to ACPA-negative patients. Additionally, the analysis demonstrates that there is no association between ACPA status and response to TNF-α-i, consistent with findings of previously published studies.
Topics: Abatacept; Anti-Citrullinated Protein Antibodies; Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Peptides, Cyclic; Treatment Outcome; Tumor Necrosis Factor Inhibitors
PubMed: 31770089
DOI: No ID Found -
BioDrugs : Clinical Immunotherapeutics,... Mar 2021Our objective was to update the understanding of the development of paradoxical immune-mediated glomerular disorders (IGDs) in patients with rheumatic diseases treated...
OBJECTIVE
Our objective was to update the understanding of the development of paradoxical immune-mediated glomerular disorders (IGDs) in patients with rheumatic diseases treated with biologics and targeted synthetic drugs (ts-drugs).
METHODS
A systematic literature review was performed by searching PubMed for articles published between 1 January 2014 and 1 January 2020 reporting on the development of IGD in adult patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or systemic lupus erythematosus (SLE) who were receiving biologics or ts-drugs. IGDs were classified on the basis of clinical, laboratory and histopathological data as (1) glomerulonephritis associated with systemic vasculitis (GNSV), (2) isolated autoimmune renal disorder (IARD) or (3) glomerulonephritis in SLE and in lupus-like syndrome (GNLS). The World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system for standardized case causality assessment was applied to evaluate the causal relationship between IGD and specific drugs. The classification was based on a six-category scale, where the "certain" and "probable" categories were deemed clinically relevant relationships.
RESULTS
The literature search retrieved 875 articles. Of these, 16 articles reported IGD data, for a total of 25 cases. According to the WHO-UMC assessment, the strength of the causal relationship between IGDs and investigated drugs was higher for anti-tumor necrosis factor-α agents (a clinically relevant relationship was found in four of six cases), abatacept (one of two cases), tocilizumab (two cases), ustekinumab (one case) and tofacitinib (one case) than for rituximab (nine cases), belimumab (three cases) or secukinumab (one case), which showed a weak causal relationship with these paradoxical events. No cases associated with apremilast or baricitinib were found. The retrieved cases were classified as 11 GNLS, seven IARD and seven GNSV.
CONCLUSIONS
Biologics and ts-drugs can cause IGDs. These events are rare, and the causative effect of a specific drug is hard to establish. When a patient is suspected of having an IGD, the drug should be discontinued, and treatment for the new-onset renal disorder should be promptly started.
Topics: Abatacept; Adult; Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Humans; Synthetic Drugs
PubMed: 33595833
DOI: 10.1007/s40259-021-00467-w -
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 -
Joint Bone Spine Jul 2021To explore current evidence on the management of poor prognostic factors in rheumatoid arthritis (RA) and to investigate whether this evidence is taken into account by...
OBJECTIVES
To explore current evidence on the management of poor prognostic factors in rheumatoid arthritis (RA) and to investigate whether this evidence is taken into account by clinicians when deciding on treatment in daily clinical practice.
METHODS
We performed a systematic literature review (SLR) to analyse the effects of currently available biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi) on the classically accepted poor prognostic factors of RA. All randomized controlled trials reporting subgroup analyses about effects on prognostic factors were identified and synthesized. In a second phase, a two-round Delphi survey was carried out to contrast the SLR results with the grade of agreement of a large group of rheumatologists about the effectiveness of each drug class on each prognostic factor.
RESULTS
According to the Delphi results, the only prognostic factor that significantly influenced the selection of treatment was the presence of interstitial lung disease (ILD), being the preferred treatment in this scenario abatacept or rituximab. The rest of the poor prognostic factors (including high disease activity at baseline, disability as measured by the Health Assessment Questionnaire index, seropositivity, elevated acute-phase reactants, and evidence of erosions based on plain radiography or ultrasonography) did not seem to significantly influence rheumatologists when choosing a treatment. The results of the SLR results did not show solid evidence regarding the use of any specific therapy in the management of patients with specific poor factors, except in the case of RA-ILD, although the data in the literature in this regard are not free of bias.
CONCLUSIONS
The only prognostic factor that seems to significantly influence the selection of treatment is the presence of RA-ILD.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Prescriptions; Prognosis; Surveys and Questionnaires
PubMed: 33689842
DOI: 10.1016/j.jbspin.2021.105172