scholarly journals Efficacy and safety of IL-17 inhibitors for the treatment of ankylosing spondylitis: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Yufeng Yin ◽  
Mingjun Wang ◽  
Mengru Liu ◽  
Erye Zhou ◽  
Tian Ren ◽  
...  

Abstract Objectives: To systematically assess the efficacy and safety of IL-17 inhibitors in patients with active ankylosing spondylitis. Methods: A systematic review of the literature was performed for randomized controlled trials (RCTs) concerning IL-17 inhibitors in patients with ankylosing spondylitis. Meta-analyses were used to determine the efficacy and safety of the IL-17 inhibitors in the treatment of these patients. The primary end point was predefined as the proportion of patients with at least 20% improvement in the Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16, and the secondary end point was defined as ASAS40 at week 16. Results: Six phase III randomized, double-blind, placebo-controlled trials including 1733 patients (1153 patients received IL-17 inhibitors, including secukinumab or ixekizumab, whereas 580 patients received a placebo as comparators) were included. At week 16, the IL-17 inhibitor regimen produced a significant increase in the ASAS20 response rate (RR=1.63, 95% CI 1.45 to 1.84, p=0.00) and the secondary endpoint ASAS40 response rate (RR=2.12, 95% CI 1.75 to 2.56, p=0.00) versus those for the placebo. With respect to the safety profile, more treatment-emergent adverse events (RR=1.11, 95% CI 1.01 to 1.22, p=0.03) and non-severe infections (RR=1.82, 95% CI 1.40 to 2.37, p<0.001) were described after treatment with IL-17 inhibitors than after treatment with placebo, while no increased risk of other adverse events was indicated after IL-17 inhibitor therapy, including death, discontinuation due to adverse events, or serious adverse events. Conclusions: IL-17 inhibitors produced favourable response rates but an increased risk of non-severe infections in the treatment of active ankylosing spondylitis.

2020 ◽  
Author(s):  
Yufeng Yin ◽  
Mingjun Wang ◽  
Mengru Liu ◽  
Erye Zhou ◽  
Tian Ren ◽  
...  

Abstract Objectives: To systematically assess the efficacy and safety of IL-17 inhibitors in patients with active ankylosing spondylitis.Methods: Electronic databases were searched for randomized controlled trials (RCTs) concerning IL-17 inhibitors in patients with ankylosing spondylitis. The efficacy and safety of the IL-17 inhibitors in the treatment of these patients were compared to those of a placebo. The primary end point was predefined as the proportion of patients with at least 20% improvement in the Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16, and the secondary end point was defined as ASAS40 at week 16.Results: Six phase III randomized, double-blind, placebo-controlled trials including 1733 patients (1153 patients received IL-17 inhibitors, including secukinumab or ixekizumab, whereas 580 patients received a placebo as comparators) were included. At week 16, the IL-17 inhibitor regimen produced a significant increase in the ASAS20 response rate (RR=1.63, 95% CI 1.45 to 1.84, p=0.00) and the secondary endpoint ASAS40 response rate (RR=2.12, 95% CI 1.75 to 2.56, p=0.00) versus those for the placebo. With respect to the safety profile, more infectious diseases were described after treatment with IL-17 inhibitors than after treatment with placebo (RR=1.82, 95% CI 1.40 to 2.37, p<0.001), while no increased risk of other adverse events was indicated after IL-17 inhibitor therapy, including treatment-emergent adverse events, death, discontinuation due to adverse event, serious adverse events, or total adverse events.Conclusions: IL-17 inhibitors produced favourable response rates but an increased risk of infectious diseases in the treatment of active ankylosing spondylitis.


2018 ◽  
Vol 19 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Mingxia Wang ◽  
Guanqi Wang ◽  
Haiyan Ma ◽  
Baoen Shan

Introduction: Crizotinib was approved to treat anaplastic lymphoma kinase (ALK)- positive non-small cell lung cancer (NSCLC) by the Food and Drug Administration in 2011.We conducted a systematic review of clinical trials and retrospective studies to compare the efficacy and safety of crizotinib with chemotherapy. </P><P> Methods: We searched electronic databases from inception to Dec. 2016. Clinical trials and retrospective studies regarding crizotinib and crizotinib versus chemotherapy in treatment of NSCLC were eligible. The primary outcomes were the objective response rate (ORR) and disease control rate (DCR). Results: Nine studies (five clinical trials and four retrospective studies) including 729 patients met the inclusion criteria. Crizotinib treatment revealed 1-year OS of 77.1% and PFS of 9.17 months. And crizotinib had a better performance than chemotherapy in ORR (OR: 4.97, 95%CI: 3.16 to 7.83, P<0.00001, I2=35%). DCR revealed superiority with crizotinib than chemotherapy (OR: 3.42, 95% CI: 2.33 to 5.01, P<0.00001, I2=0%). PR (partial response) were significant superior to that of chemotherapy through direct systematic review. No statistically significant difference in CR (complete response) was found between crizotinib-treated group and chemotherapy-treated group. Regarding SD (stable disease), chemotherapy-treated group had a better performance than crizotinib-treated group. Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, nausea, and hematologic toxicity. This systematic review revealed improved objective response rate and increased disease control rate in crizotinib group comparing with chemotherapy group. Crizotinib treatment would be a favorable treatment option for patients with ALK-positive NSCLC. ALK inhibitors may have future potential applications in other cancers driven by ALK or c-MET gene mutations.


2021 ◽  
pp. 10.1212/CPJ.0000000000001143
Author(s):  
Glenardi Glenardi ◽  
Tutwuri Handayani ◽  
Jimmy Barus ◽  
Ghea Mangkuliguna

ABSTRACTPurposeof Review: To investigate the efficacy and safety of CVT-301 for motor fluctuation in Parkinson’s disease (PD).Recent Findings:This study demonstrated that the CVT-301 group had a higher proportion of patients achieving an ON state than the placebo group (OR=2.68; 95% CI: 1.86-3.86; p<0.00001). Moreover, CVT-301 had also shown to improve motor function by UPDRS-III score (SMD=3.83; 95% CI: 2.44-5.23; p<0.00001) and promote an overall improvement of PD by PGIC self-rating (OR=2.95; 95% CI: 1.78-4.9; p<0.00001). The most common adverse events encountered were respiratory symptoms (OR=12.18; 95% CI: 5.01-29.62; p<0.00001) and nausea (OR=3.95; 95% CI: 1.01-15.41; p=0.05).Summary:CVT-301 had the potential to be an alternative or even a preferred treatment for motor fluctuation in PD patients.


BMJ Open ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. e047344
Author(s):  
Qingwu Wu ◽  
Lianxiong Yuan ◽  
Huijun Qiu ◽  
Xinyue Wang ◽  
Xuekun Huang ◽  
...  

ObjectivesTo assess the efficacy and safety of omalizumab for chronic rhinosinusitis with nasal polyps (CRSwNP) and to identify evidence gaps that will guide future research on omalizumab for CRSwNP.DesignSystematic review and meta-analysis.Data sourcesA comprehensive search was performed in PubMed, Embase, Web of Science and the Cochrane Library on 13 October 2020.Eligibility criteriaRandomised controlled trials (RCTs) comparing omalizumab with placebo, given for at least 16 weeks in adult patients with CRSwNP.Data extraction and synthesisTwo independent authors screened search results, extracted data and assessed studies using the Cochrane risk of bias tool. Data were pooled using the inverse-variance method and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed by the χ2 test and the I2 statistic.ResultsA total of four RCTs involving 303 participants were identified. When comparing omalizumab to placebo, there was a significant difference in Nasal Polyps Score (MD=−1.20; 95% CI −1.48 to −0.92), Nasal Congestion Score (MD=−0.67; 95% CI −0.86 to −0.48), Sino-Nasal Outcome Test-22 (MD=−15.62; 95% CI −19.79 to −11.45), Total Nasal Symptom Score (MD=−1.84; 95% CI −2.43 to −1.25) and reduced need for surgery (risk ratio (RR)=5.61; 95% CI 1.99 to 15.81). Furthermore, there was no difference in the risk of serious adverse events ((RR=1.40; 95% CI 0.29 to 6.80), adverse events (RR=0.83; 95% CI 0.60 to 1.15) and rescue systemic corticosteroid (RR=0.52; 95% CI 0.17 to 1.61).ConclusionsThis was the first meta-analysis that identified omalizumab significantly improved endoscopic, clinical and patient-reported outcomes in adults with moderate to severe CRSwNP and it was safe and well tolerated.PROSPERO registration numberCRD42020207639.


BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e050004
Author(s):  
Wenjuan Wu ◽  
Lingxiao Qiu ◽  
Jizhen Wu ◽  
Xueya Liu ◽  
Guojun Zhang

ObjectivesIdiopathic pulmonary fibrosis (IPF) has been defined as a distinctive type of chronic fibrotic disease, characterised by a progressive decline in lung function and a common histological pattern of interstitial pneumonia. To analyse the efficacy and safety of pirfenidone in the treatment of IPF, a systematic review and meta-analysis was performed.DesignThis is a meta-analysis study.ParticipantsPatients were diagnosed as IPF.InterventionsUse of pirfenidone.Primary and secondary outcomeProgression-free survival (PFS), acute exacerbation and worsening of IPF and Impact on adverse events.MeasuresThe inverse variance method for the random-effects model was used to summarise the dichotomous outcomes, risk ratios and 95% CIs.ResultsA total of 9 randomised controlled trials with 1011 participants receiving pirfenidone and 912 controls receiving placebo were summarised. The pooled result suggested a statistically significant difference inall-cause mortality after pirfenidone use, with a summarised relative ratio of 0.51 (p<0.01). Longer PFS was observed in patients receiving pirfenidone compared with those who were given placebo (p<0.01). The IPF groups presented a high incidence of adverse events with a pooled relative ratio of 3.89 (p<0.01).ConclusionsPirfenidone can provide survival benefit for patients with IPF. Pirfenidone treatment was also associated with a longer PFS, a lower incidence of acute exacerbation and worsening of IPF.


2015 ◽  
Vol 24 (1) ◽  
pp. 44-49
Author(s):  
Claudiu Popescu ◽  
◽  
Cristina Coroama ◽  
Costin Mitulescu ◽  
Denisa Predeteanu ◽  
...  

Rationale. Data from controlled trials showed that adalimumab, a humanized anti-TNF monoclonal antibody, is effective and safe in the treatment of ankylosing spondylitis (AS). Objectives. The present study aimed to observe the effi cacy and safety of adalimumab in AS in a real life clinical setting. Methods. The study observed cross-sectionaly and retrospectively the efficacy and safety of adalimumab in all the patients admitted to the Rheumatology Department of “Sfânta Maria” Clinical Hospital between January 2008 and June 2013 who were classified as having AS according to the modified New York criteria. The diagnosis and follow-up of uveitic cases were done in the Ophthalmology Department of the Emergency University Hospital. Results. Within the study time-frame, 79 AS patients met the inclusion criteria: 71 (89.9%) had adalimumab for at least 24 months; 8 (10.1%) switched from adalimumab to another biological, as follows: 3 (3.8%) because of serious adverse events, 3 (3.8%) were primary non-responders and 2 (2.5%) were secondary non-responders. The clinical response was fast: after 3 months of treatment, 59 (83.1%) patients had BASDAI < 4 and 55 (77.5%) patients had BASFI < 4. Regarding safety, the serious adverse effects recorded were: infectious arthritis, pulmonary tuberculosis, pulmonary sarcoidosis. There were no cases of cancer or demyelinating disease during the study frame. Conclusions. Therapy with adalimumab in AS produces a prompt and lasting effect. The efficacy (remission) and safety (adverse events) of adalimumab can be monitored in the real-life clinical setting using BASDAI, BASFI, and routine clinical evaluations. Clinicians may need to expect a slightly higher rate of serious adverse events and rate of treatment discontinuation than those reported by controlled trials.


2021 ◽  
Vol 15 ◽  
Author(s):  
Xinglin Ruan ◽  
Fabin Lin ◽  
Dihang Wu ◽  
Lina Chen ◽  
Huidan Weng ◽  
...  

Background: Movement fluctuations are the main complication of Parkinson's disease (PD) patients receiving long-term levodopa (L-dopa) treatment. We compared and ranked the efficacy and safety of dopamine agonists (DAs) with regard to motor fluctuations by using a Bayesian network meta-analysis (NMA) to quantify information from randomized controlled trials (RCTs).Methods and Findings: We carried out a systematic review and meta-analysis, and only RCTs comparing DAs for advanced PD were included. Electronic databases (PubMed, Embase, and Cochrane Library) were systematically searched for relevant studies published until January 2021. Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Network meta-analyses using a Bayesian framework were used to calculate the related parameters. The pre-specified primary and secondary outcomes were efficacy (“ON” time without troublesome dyskinesia, “OFF” time, “ON” time, “UPDRS-III,” and “UPDRS-II”) and safety [treatment-emergent adverse events (TEAE) and other adverse events] of DAs. The results are presented as the surface under the cumulative ranking (SUCRA) curve. A total of 20 RCTs assessing 6,560 patients were included. The general DA effects were ranked from high to low with respect to the amount of “ON” time without troublesome dyskinesia as follows: apomorphine (SUCRA = 97.08%), pramipexole_IR (probability = 79.00%), and ropinirole_PR (SUCRA = 63.92%). The general safety of DAs was ranked from high to low with respect to TEAE as follows: placebo (SUCRA = 74.49%), pramipexole_ER (SUCRA = 63.6%), sumanirole (SUCRA = 54.07%), and rotigotine (SUCRA = 53.84%).Conclusions: This network meta-analysis shows that apomorphine increased “ON” time without troublesome dyskinesia and decreased “OF” time for advanced PD patients. The addition of pramipexole, ropinirole, or rotigotine to levodopa treatment in advanced PD patients with motor fluctuations increased “ON” time without troublesome dyskinesia, improved the UPDRS III scores, and ultimately ameliorated the UPDRS II scores, thereby maximizing its benefit. This NMA of pramipexole, ropinirole, and rotigotine represents an effective treatment option and has an acceptable safety profile in patients with advanced PD.


2020 ◽  
Author(s):  
Xiaojing Yi ◽  
Yun Chen ◽  
Kun Chen ◽  
Mo Liu ◽  
Jiale Yi ◽  
...  

Abstract Background: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are a novel class of drugs for migraine that includes erenumab, fremanezumab, galcanezumab and eptinezumab. In clinical trials, CGRP mAbs have been reported to show good efficacy in the prevention of episodic migraines or chronic migraines. Our aim was to evaluate the efficacy and safety of CGRP monoclonal antibodies in this study.Methods: We systematically searched for randomized controlled trials in the PubMed, Embase, ClinicalTrials.gov, and Cochrane Library databases. The primary outcome was overall mean change from baseline to end of treatment in the number of monthly migraine headache days (MMHDs). The secondary outcomes included 50% response rate, in the number of monthly headache days (MHDs), in the number of monthly headache hours (MHHs), and in the number of monthly acute migraine-specific medication days (MSMDs). The safety outcomes were evaluated in terms of reported adverse events. Results: Eighteen studies including 11,099 patients were included in the meta-analysis. The meta-analysis showed that CGRP mAbs exhibited a significant benefit in reducing the number of MMHDs compared to placebo (Episodic migraine: Std. MD -0.42, 95% CI -0.47 to -0.36; Chronic migraine: Std. MD -0.28, 95% CI -0.35 to -0.21). Similarly, CGRP mAbs were superior to placebo in the secondary outcomes of 50% response rate, MHDs, MHHs, and MSMDs. With respect to safety, serious adverse events and withdrawal due to adverse events were not significantly associated with CGRP mAbs. Fremanezumab was associated with a significantly higher incidence of any adverse event compared with placebo (RR 1.10, 95% CI 1.03 to 1.17). Galcanezumab was associated with significantly higher treatment-emergent adverse events compared with placebo (RR 1.11, 95% CI 1.04 to 1.17). Constipation and injection site pain were significantly higher with erenumab than placebo. Injection site erythema and injection site induration were significantly higher with fremanezumab than placebo. Upper respiratory tract infection, injection site erythema, injection site pruritus and injection site reaction were significantly higher with galcanezumab than placebo. Conclusions: This study confirms that CGRP mAbs are effective as preventive treatments for episodic migraines and chronic migraines. Adverse reactions at the injection site were associated with erenumab, fremanezumab and galcanezumab therapy. Constipation was more common with erenumab. The risk of upper respiratory tract infection was higher with galcanezumab.Systematic review registration: Our PROSPERO protocol registration number: CRD42019125928. Registered 26 November 2019.


Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1020
Author(s):  
Ching-Yi Chen ◽  
Wang-Chun Chen ◽  
Chih-Cheng Lai ◽  
Tzu-Ping Shih ◽  
Hung-Jen Tang

This systematic review and meta-analysis of randomized controlled trials (RCTs) compared the clinical efficacy and safety of anti-MRSA cephalosporin and vancomycin-based treatment in treating acute bacterial skin and skin structure infections (ABSSSIs). PubMed, Embase, Cochrane Central Register of Controlled Trials, Turning Research into Practice, and ClinicalTrials.gov databases were searched for relevant articles from inception to 15 June 2020. RCTs comparing the clinical efficacy and safety of anti-MRSA cephalosporin with those of vancomycin-based regimens in treating adult patients with ABSSSIs were included. The primary and secondary outcomes were clinical response at the test-of-cure assessments and risk of adverse events (AEs), respectively. Eight RCTs were enrolled. The clinical response rate was not significantly different between anti-MRSA cephalosporin and vancomycin-based treatments (odds ratio [OR], 1.05; 95% CI, 0.90–1.23; I2 = 0%). Except for major cutaneous abscesses in which anti-MRSA cephalosporin-based treatment was associated with a lower clinical response rate than vancomycin-based treatment (OR, 0.62; 95% CI, 0.40–0.97; I2 = 0%), other subgroup analyses according to the type of cephalosporin (ceftaroline or ceftobiprole), type of infection, and different pathogens did not show significant differences in clinical response. Anti-MRSA cephalosporin-based treatment was only associated with a higher risk of nausea than vancomycin-based treatment (OR, 1.41; 95% CI, 1.07–1.85; I2 = 0%). In treating ABSSSIs, the clinical efficacy of anti-MRSA cephalosporin is comparable to that of vancomycin-based treatment, except in major cutaneous abscesses. In addition to nausea, anti-MRSA cephalosporin was as tolerable as vancomycin-based treatment.


2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Yichen Xuan ◽  
Hui Huang ◽  
Yiyong Huang ◽  
Duanyong Liu ◽  
Xiuwu Hu ◽  
...  

Background. Clinical investigators have found that the use of needling in the treatment of ankylosing spondylitis (AS) has a good clinical application prospect in recent years. However, these studies were insufficient to provide evidence for the efficacy and safety of simple-needling for AS. So, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of simple-needling for treating AS. Methods. We searched the PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Wangfang database (Wanfang), Chinese Science and Technology Periodical Database (VIP), and any other gray literature sources for randomized controlled trials (RCTs) that used simple-needling to treat AS before June 2019 with the language restriction of Chinese and English. Researchers evaluated the retrieved literature studies and extracted valid data according to relevant requirements and used RevMan5.3 software for meta-analysis. Results. A total of 10 studies were included, all of which were Chinese literature studies, involving 729 patients. Compared with the control groups, simple-needling groups had a better effect on the clinical effective rate (RR = 1.20, 95% CI (1.11, 1.29), P<0.00001), TCM syndrome score (MD = −5.26, 95% CI (−5.99, −4.53), P<0.00001), symptom score (MD = −8.08, 95% CI (−10.18, −5.97), P<0.00001), and Schober test outcome (MD = 0.39, 95% CI (0.15, 0.64), P=0.002). Sensibility analysis was based on the leave-one-out cross-validation procedure, and the results showed no significant changes. Most studies did not describe adverse reactions. The funnel plot suggested publication bias on clinical effectiveness. Conclusions. This systematic review and meta-analysis demonstrated that simple-needling was effective as an intervention for AS. However, due to the low quality of the methodology of included studies, the designs of clinical trials were not rigorously standardized. Therefore, it is necessary to carry out multiquality RCTs for verification.


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