The objective of this systematic review is to determine the effects of IL-17 inhibitors on major adverse cardiovascular events (MACEs) in patients with either psoriasis (PsO) or psoriatic arthritis (PsA). A systematic literature search in three databases (Medline, Embase, and the Cochrane Library for Randomized Controlled Trials) was conducted on December 7, 2022 for randomized controlled trials of patients with PsO/PsA treated with IL-17 inhibitors that reported confirmed MACEs. Two reviewers screened titles and abstracts and identified papers for full-text review. Exclusion criteria included trials that included the previous use of biological disease-modifying anti-rheumatic drugs. The Mantel-Haenszel random-effect method was utilized to calculate risk ratios and heterogeneity was measured by χ2 test and I2 statistics. Funnel plot analysis was undertaken to detect potential publication bias. Of the 919 references identified, nine RCT studies were included in the meta-analysis (n=2,096 patients). There was no statistically significant correlation between the use of IL-17 inhibitors and change in risk of MACEs (Risk Ratio 0.56; 95% CI 0.15 to 2.14; p = 0.40). Subgroup analysis of secukinumab or ixekizumab also did not demonstrate these changes. Additionally, there was no detectable dose-dependent effect of IL-17 inhibitors. In conclusion, IL-17 inhibitor use is not correlated with a change in MACE risk in patients with PsO/PsA who previously did not receive biologic disease-modifying anti-rheumatic drugs.
BACKGROUND AND AIMS: Recent studies raise concern for increased risk of major adverse cardiovascular events (MACE) with Janus kinase inhibitors (JAKi) used to treat immune-mediated inflammatory disorders (IMIDs). We aimed to examine MACE risk with licensed biologics and small molecules used commonly between IMIDs: inflammatory bowel disease, rheumatoid arthritis, psoriasis/psoriatic arthritis, and ankylosing spondylitis.
METHODS: Data were obtained from systematic searches (from inception to May 31, 2022) in PubMed, Embase, Ovid Medline, Scopus, Cochrane Central, and Clinicaltrials.gov. Studies that assessed a pre-defined MACE (myocardial infarction, cerebrovascular accident, unstable angina, cardiovascular death, or heart failure) risk in those ≥18 years with IMIDs treated with anti-interleukin (IL)-23 antibodies, anti-IL-12/23, anti-tumor necrosis factor-alpha antibodies (anti-TNF-α) or JAKi were included in a network meta-analysis using a random-effects model with pooled odds ratios (ORs) reported with 95% credible intervals (CrIs) by drug class and disease state.
RESULTS: Among 3,528 studies identified, 40 (36 randomized controlled trials [RCTs] and 4 cohort studies) were included in the systematic review, comprising 126,961 patients with IMIDs. Based on network meta-analysis of RCTs, regardless of disease state, anti-TNF-α (OR, 2.49; CrI: 1.14-5.62), JAKi (OR, 2.64; CrI: 1.26-5.99), and anti-IL-12/23 (OR, 3.15; CrI: 1.01-13.35) were associated with increased MACE risk compared with placebo. There was no significant difference in the magnitude of the MACE risk between classes or based on IMID type.
CONCLUSIONS: Anti-IL-12/23, JAKi, and anti-TNF-α were associated with higher risk of MACE compared with placebo. The magnitude of the increased MACE risk was not different by IMID type. These results require confirmation in larger prospective studies.
OBJECTIVES: To evaluate the efficacy and safety of Janus kinase (JAK) inhibitors (Jakinibs) in the treatment of psoriasis and psoriatic arthritis (PsA).
METHODS: Databases including PubMed, Embase, Web of Science, and Cochrane Library were searched for randomized controlled trials on the efficacy and safety of Jakinibs in treating psoriasis and PsA from inception to July 2021. A systematic review and meta-analysis were performed to estimate pooled relative risk (RR) and 95% confidence interval (CI).
RESULTS: Seventeen clinical trials (16 publications) comprising 6802 patients were included. All Jakinibs demonstrated significantly higher response rates compared with placebo (ACR20: RR 2.09, 95% CI 1.90-2.30; PASI75: RR 4.03, 95% CI 3.13-5.18). Within the subgroup analysis, the response rates defined by ACR20 were highest for filgotinib (RR 2.40, 95% CI 1.67-3.45), followed by upadacitinib, tofacitinib, and deucravacitinib. The proportion of patients achieving PASI75 response in the tofacitinib 10 mg twice daily group was significantly higher than that in the tofacitinib 5 mg group. Regarding safety, the incidence of adverse events (AEs) was significantly higher for Jakinibs compared with placebo (RR 1.17, 95% CI 1.11-1.23). Of note, a considerable increase in the risk of infections including upper respiratory tract and herpes zoster infection was observed among patients in the treatment group. For tofacitinib, upadacitinib, and filgotiniband, infection was the most prevalent AE. Moreover, AEs in the 10 mg tofacitinib group were higher than those in the 5 mg tofacitinib group.
CONCLUSION: Jakinibs are efficacious interventions for the treatment of psoriasis and PsA, but they are associated with an increased risk of AEs when compared with placebo. The long-term efficacy and safety data require further evaluation. Key Points • This systematic review investigated and compared the efficacy and safety of different Jakinibs including the novel selective TYK2 inhibitors. • Jakinibs are efficacious interventions for the treatment of psoriasis and PsA. • A relatively higher dosing schedule of Jakinibs is associated with increased toxicity.
This study aims to estimate the effect of synthetic and biologic disease-modifying antirheumatic drugs (DMARDs) on radiographic progression and quality of life in adult patients with psoriatic arthritis. A comprehensive search was performed using MEDLINE, Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials (CCRCT). Clinical trials comparing DMARDs with placebo for ≥ 12 weeks were included. The meta-analysis was conducted with a random-effects model using mean differences (MD). A total of 16 trials with overall moderate quality of evidence were included. Exposure to a biologic agent reduced radiographic progression at 24 weeks of treatment (MD: - 0.66; [95% CI - 0.97 to - 0.34]; P < .00001; I2 = 100%). The reduction of the baseline score was more than two times higher for TNF blockers compared with IL-17 and IL-12/IL-23 inhibitors (MD: - 0.94 vs - 0.41). Improvement in health-related quality of life scores was observed in biologic-treated populations (MD: - 0.21; [95% CI - 0.25 to - 0.18]; P < .00001; I2 = 97%). No sufficient data were available regarding conventional synthetic agents. Our data analyses suggest a better control of radiological damage with bDMARDs, as compared to placebo, after 24 weeks of treatment. However, the accuracy of these results in real life are jeopardized by the exceedingly high level of heterogeneity exhibited within and across included studies, and the true intervention effect cannot be determined with confidence. Further research is required to assess long-term outcomes and to control heterogeneity in the evaluation of treatments for psoriatic arthritis. PROSPERO registration number: CRD42019122223. Key Points • Radiographic progression is not the primary outcome for most efficacy studies in psoriatic arthritis; hence, baseline data are substantially diverse in major clinical trials. • The best available evidence on this particular outcome is currently at a moderate risk of bias. • Existing reports of the effect of DMARDs on structural damage must be taken with caution. • Further research is required to assess long-term outcomes and to control heterogeneity between studies.
The objective of our study was to compare a potent drug of the anti-TNF class family, infliximab, with a potent drug of the IL-inhibitors family, risankizumab, in terms of efficacy and safety endpoints. Online databases were searched for relevant placebo-controlled, randomized trials. The following efficacy outcomes were included: PASI-75, PASI-90, and sPGA, as well as the incidence of any adverse events and serious adverse events. The risk ratios (RR) with the respective 95% confidence intervals (CIs) of different psoriasis scores were pooled in a meta-analysis model, using the Mantel-Haenszel method. The combined risk ratios (RR) showed that infliximab and risankizumab are effective in increasing the number of patients with more than 75% improvement in the PASI (RR= 26.68, 95% CI [14.98, 47.51] p<0.001) and (RR= 10.17, 95% CI [7.24, 14.30] p<0.001), respectively. Test for subgroup differences showed that risankizumab is more effective. Regarding PASI-90 outcome, risankizumab and infliximab are more effective than placebo (RR= 26.22, 95% CI [14.20, 48.41], p<0.001), and (RR= 15.18, 95% CI [8.72, 26.45], p<0.001) respectively. The results showed that risankizumab does not cause significant serious adverse events (RR = 0.59, 95% CI [0.31, 1.13], p=0.12) while, on the other hand, infliximab causes significant serious adverse events (RR = 2.30, 95% CI [1.08, 4.88], p=0.03). The test of subgroup difference showed that risankizumab is safer (p<0.001). Analysis of the incidence of any adverse events showed that risankizumab is safer as well (p=0.007). Infection rates were similar among both drugs (p=0.05). In conclusion, risankizumab is preferred for the treatment of psoriasis than infliximab, and is significantly more effective and safe.
WHAT IS KNOWN AND OBJECTIVE: To assess the efficacy and safety of interleukin-17 inhibitors (ixekizumab, secukinumab, bimekizumab, netakimab and brodalumab) in chronic inflammatory rheumatic diseases, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA).
METHODS: A comprehensive search for randomized controlled trials (RCTs) evaluating efficacy and safety of interleukin-17 inhibitors was performed through PubMed, Embase and Cochrane Library databases. Quality assessment was performed using the Cochrane Collaboration risk of bias tool. Data were pooled using the fixed or random-effects models.
RESULTS AND DISCUSSION: Twenty RCTs were identified: of these 9 studies on patients with AS and 11 studies on patients with PsA. Concerning clinical efficacy, a pooled analysis showed interleukin-17 inhibitors had a higher response rate for the primary endpoint (p < 0.05) and secondary endpoint (p < 0.05) at the treatment endpoint for AS/PsA patients. Moreover, an increased risk of treatment-emergent adverse events and infection was found in AS patients (p < 0.05). In contrast, no increased risk of any adverse events was reported in PsA patients.
WHAT IS NEW AND CONCLUSION: In this meta-analysis, our findings found interleukin-17 inhibitors had a significant clinical benefit in the management of AS/PsA patients.
Purpose: Tofacitinib citrate is an oral Janus kinase 1/3 inhibitor approved for rheumatoid arthritis, ulcerative colitis, and active psoriatic arthritis. Tofacitinib is being increasingly used off-label for dermatological conditions, with varying efficacy across recent studies. A review of these studies will be a helpful resource for dermatologists considering the use of tofacitinib for conditions refractory to first-line therapies. Materials and methods: MEDLINE, Embase, CINAHL Plus, Cochrane Library, Scopus, Web of Science, Clinicaltrials.gov, and the WHO International Clinical Trials Registry Platform were all searched for articles and trials mentioning the term 'tofacitinib', then manually reviewed to identify published data on off-label uses of tofacitinib. The article was structured according to the quality of the evidence available. Results: Tofacitinib appears to show strong efficacy for numerous dermatologic conditions. Randomized controlled trial data is available for atopic dermatitis, alopecia areata, and plaque psoriasis. Case report and case series data is available for numerous other dermatologic conditions. Conclusion: While tofacitinib has a wide array of immunoregulatory properties, making it a possible candidate for treating many dermatologic conditions refractory to other treatments, further testing is needed to better characterize its efficacy and utility moving forward, as well as its safety and adverse effect profile.
INTRODUCTION: Therapeutic approaches for psoriatic arthritis (PsA) include non-pharmacologic therapies, symptomatic treatments, tumor necrosis factor inhibitors, interleukin inhibitors, cytotoxic T lymphocyte antigen 4 immunoglobulin, and Janus kinase inhibitors. This systematic review aimed to provide complete and up-to-date information on efficacy of tofacitinib in the treatment of PsA, giving special attention to non-skin manifestations (peripheral arthritis, axial disease, enthesitis, and dactylitis).
METHODS: A search of studies published between January 2016 and June 2020 was carried out on PubMed and Google Scholar.
RESULTS: The number of studies with tofacitinib in PsA is limited and most of them are post hoc analyses from OPAL Broaden and OPAL Beyond. Tofacitinib has been demonstrated to be efficacious for the treatment of all disease manifestations in PsA. Superior effectivity to placebo is achieved at the earliest time point evaluated, and maintained over time. Patients who switch from placebo to tofacitinib show the same improvements; however, the time to initial response is faster in patients who firstly receive tofacitinib, compared with those switching subsequently. Additional data suggest that tofacitinib may be also effective for the treatment of the axial domain.
CONCLUSIONS: Tofacitinib has been demonstrated to be efficacious for the treatment of peripheral and axial involvement, enthesitis, and dactylitis manifestation in PsA. Further prospective and long-term studies are required to corroborate and complete the present results. Similarly, real-world evidence is also necessary to complement the information obtained in clinical trials, and thereby to have a better overview of real efficacy and safety of the drug.
The objective of this systematic review is to determine the effects of IL-17 inhibitors on major adverse cardiovascular events (MACEs) in patients with either psoriasis (PsO) or psoriatic arthritis (PsA). A systematic literature search in three databases (Medline, Embase, and the Cochrane Library for Randomized Controlled Trials) was conducted on December 7, 2022 for randomized controlled trials of patients with PsO/PsA treated with IL-17 inhibitors that reported confirmed MACEs. Two reviewers screened titles and abstracts and identified papers for full-text review. Exclusion criteria included trials that included the previous use of biological disease-modifying anti-rheumatic drugs. The Mantel-Haenszel random-effect method was utilized to calculate risk ratios and heterogeneity was measured by χ2 test and I2 statistics. Funnel plot analysis was undertaken to detect potential publication bias. Of the 919 references identified, nine RCT studies were included in the meta-analysis (n=2,096 patients). There was no statistically significant correlation between the use of IL-17 inhibitors and change in risk of MACEs (Risk Ratio 0.56; 95% CI 0.15 to 2.14; p = 0.40). Subgroup analysis of secukinumab or ixekizumab also did not demonstrate these changes. Additionally, there was no detectable dose-dependent effect of IL-17 inhibitors. In conclusion, IL-17 inhibitor use is not correlated with a change in MACE risk in patients with PsO/PsA who previously did not receive biologic disease-modifying anti-rheumatic drugs.
Pregunta de la revisión sistemática»Revisión sistemática de intervenciones
