scholarly journals Efficacy and Safety of Remdesivir for COVID-19 Treatment: An Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

2020 ◽  
Author(s):  
Yun Zhu ◽  
Zhaowei Teng ◽  
Lirong Yang ◽  
Shuanglan Xu ◽  
Jie Liu ◽  
...  
Keyword(s):  
Adverse Events ◽  
Discharge Rate ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Randomized Controlled ◽  
Central Register ◽  
Registration Number

AbstractBACKGROUNDRemdesivir, an inhibitor of viral RNA-dependent RNA polymerases, has been identified as a candidate for COVID-19 treatment. However, the therapeutic effect of remdesivir is controversial.METHODSWe searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, from inception to June 11, 2020 for randomized controlled trials on the clinical efficacy of remdesivir. The main outcomes were discharge rate, mortality, and adverse events. This study is registered at INPLASY (INPLASY202060046).RESULTSData of 1075 subjects showed that remdesivir significantly increased the discharge rate of patients with COVID-19 compared with the placebo (50.4% vs. 45.29%; relative risk [RR] 1.19 [95% confidence interval [CI], 1.05–1.34], I2 = 0.0%, P = 0.754). It also significantly decreased mortality (8.18% vs. 12.70%; RR 0.64 [95% CI, 0.44–0.92], I2 = 45.7%, P = 0.175) compared to the placebo. Data of 1296 subjects showed that remdesivir significantly decreased the occurrence of serious adverse events (RR 0.77 [95% CI, 0.63–0.94], I2 = 0.0%, P = 0.716).CONCLUSIONRemdesivir is efficacious and safe for the treatment of COVID-19.TRIAL REGISTRATION NUMBERThis study is registered at the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY202060046).

Immune-related adverse events and efficacy outcomes in patients treated with immunotherapy: A systematic review and meta-analysis.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 92-92
Author(s):  
Eric Druyts ◽  
Mark Boye ◽  
Himani Agg ◽  
Catherine Muehlenbein ◽  
Andrew Frederickson ◽  
...  
Keyword(s):  
Systematic Review ◽  
Head And Neck Cancer ◽  
Adverse Events ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Efficacy Data ◽  
Incidence Data ◽  
Randomized Controlled ◽  
Central Register

92 Background: Immunotherapy (IO) can lead to immune-related adverse events (irAEs). Evidence on the association of irAEs and efficacy is limited. Methods: We conducted a systematic review in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (inception to July 1, 2019) to identify randomized controlled trials (RCTs) reporting irAEs, incidence and efficacy data for pembrolizumab (PEM), nivolumab (NIVO), ipilimumab (IPI), atezolizumab, avelumab, durvalumab, and aldesleukin in lung, renal, head and neck cancer, and melanomas. RCTs assessing IO monotherapy or IO combinations in at least one arm were included. Evaluated outcomes were 1) irAE incidence (rash, pruritis, diarrhea, colitis, hypothyroidism, hyperthyroidism, transaminitis, hypophysitis, pneumonitis, arthralgia, anemia, and hepatitis); and 2) efficacy (response and survival). irAE incidence data will be pooled and meta-analysis performed to assess the association of irAEs with efficacy; heterogeneity between RCTs will be evaluated. Results: Fifty RCTs were included: IOs were compared to chemotherapy or chemotherapy-combinations (19), to other interventions (8), to placebo (3), and head-to-head (20). irAE reporting and definitions were heterogeneous across RCTs. The most common all-grade irAEs were skin, GI, and endocrine. For skin irAEs, rash ranged from 0% (PEM 2 mg/kg, n = 6) to 73% (NIVO + IPI, n = 11); pruritus was from 1% (PEM 2 mg/kg, n = 89) to 50% (NIVO + IPI, n = 6). For GI irAEs, diarrhea ranged from 0% (PEM 2 mg/kg, n = 6) to 64% (NIVO + IPI, n = 11); colitis was from 0% (NIVO 3 mg/kg, n = 98) to 23% (NIVO + IPI, n = 94). For endocrine irAEs, hypothyroidism ranged from 0% (NIVO 3 mg/kg, n = 12) to 83% (NIVO + IPI, n = 6), hyperthyroidism was from 0% (PEM 2 mg/kg, n = 6 and IPI 3 mg/kg, n = 46) to 27% (NIVO + IPI, n = 11), and hypophysitis was from 0% (PEM 10 mg/kg, n = 84 and NIVO 3 mg/kg, n = 25) to 26% (NIVO + IPI, n = 35). Liver, pulmonary, and musculoskeletal irAEs, and anemia, were reported less frequently and with lower incidence. Conclusions: irAEs are increasingly reported in IO RCTs, but lack reporting and definition consistency. The meta-analysis results may provide clarity on irAEs incidence and association with efficacy.

Leflunomide Use and Risk of Lung Disease in Rheumatoid Arthritis: A Systematic Literature Review and Metaanalysis of Randomized Controlled Trials

2016 ◽  
Vol 43 (5) ◽  
pp. 855-860 ◽  
Author(s):  
Richard Conway ◽  
Candice Low ◽  
Robert J. Coughlan ◽  
Martin J. O’Donnell ◽  
John J. Carey
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Lung Disease ◽  
Randomized Controlled Trials ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Double Blind ◽  
Randomized Controlled ◽  
Central Register ◽  
Increased Risk

Objective.To evaluate the relative risk (RR) of pulmonary disease among patients with rheumatoid arthritis (RA) treated with leflunomide (LEF).Methods.We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials to April 15, 2014. We included double-blind randomized controlled trials (RCT) of LEF versus placebo or active comparator agents in adults with RA. Studies with fewer than 50 subjects or shorter than 12 weeks were excluded. Two investigators independently searched both databases. All authors reviewed selected studies. We compared RR differences using the Mantel-Haenszel random-effects method to assess total respiratory adverse events, infectious respiratory adverse events, noninfectious respiratory adverse events, interstitial lung disease, and death.Results.Our literature search returned 5673 results. A total of 8 studies, 4 with placebo comparators, met our inclusion criteria. There were 708 respiratory adverse events documented in 4579 participants. Six cases of pneumonitis occurred, all in the comparator group. Four pulmonary deaths were reported, none in the LEF group. LEF was not associated with an increased risk of total adverse respiratory events (RR 0.99, 95% CI 0.56–1.78) or infectious respiratory adverse events (RR 1.02, 95% CI 0.58–1.82). LEF was associated with a decreased risk of noninfectious respiratory adverse events (RR 0.64, 95% CI 0.41–0.97).Conclusion.Our study found no evidence of increased respiratory adverse events in RCT of LEF treatment.

Pharmacological Treatment of Osteoporosis in Elderly People: A Systematic Review and Meta-Analysis

Gerontology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Qin-Yi Wang ◽  
Na Ding ◽  
Yi-He Dong ◽  
Zhang-Xin Wen ◽  
Rong Chen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Elderly Patients ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Anabolic Agents ◽  
Double Blind ◽  
Antiresorptive Agents ◽  
Statistical Heterogeneity ◽  
Post Hoc

<b><i>Background:</i></b> The evidence supporting the use of antiresorptive and anabolic agents for fracture prevention in elderly patients is still inconclusive. Whether it is too late to alter the course of the disease in this age-group has remained uncertain. <b><i>Objectives:</i></b> The objective of this study was to determine the efficacy and safety of antiresorptive and anabolic agents in elderly patients. <b><i>Methods:</i></b> PubMed, Web of Science, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) and post hoc analyses of RCTs reporting efficacy outcomes or adverse events of antiresorptive and anabolic agents in elderly patients. Statistical heterogeneity was assessed with the Cochran <i>Q</i> χ<sup>2</sup> test and <i>I</i><sup>2</sup> statistic. All results were expressed as relative risk (RR) with 95% confidence intervals (CIs). <b><i>Results:</i></b> The meta-analysis included 1 RCT and 11 post hoc analyses of data from 10 double-blind placebo-controlled RCTs. Antiresorptive therapy significantly reduced the pooled incidence of vertebral fractures (RR = 0.43; 95% CI = 0.35–0.53; and <i>p</i> &#x3c; 0.001). It was also associated with lower risk of nonvertebral and hip fractures (RR = 0.84; 95% CI = 0.74–0.96; and <i>p</i> = 0.009 and RR = 0.75; 95% CI = 0.58–0.97; and <i>p</i> = 0.028, respectively). For any adverse events, no difference was observed between antiresorptive agents and placebo groups (RR = 1.01; 95% CI = 1.00–1.02; and <i>p</i> = 0.23). <b><i>Conclusions:</i></b> Both antiresorptive and anabolic agents represented potentially important osteoporosis treatments, showing significant effects on reducing vertebral, nonvertebral, or hip fracture risk, and were well-tolerated by elderly patients. Even in the elderly, maybe it is not too late to alter the course of the disease.

scholarly journals The efficacy and safety of intrathecal bupivacaine alone versus bupivacaine combined with magnesium sulfate in adults using spinal anesthesia: a meta-analysis of randomized controlled trials

2020 ◽  
Author(s):  
Mi-Zhou Wang ◽  
Rui Dong ◽  
Li-Na Jia ◽  
Deng-Bin Ai ◽  
Jian-Hua Zhang
Keyword(s):  
Adverse Events ◽  
Randomized Controlled Trials ◽  
Magnesium Sulfate ◽  
Motor Block ◽  
Meta Analysis ◽  
Sensory Block ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Rescue Analgesia ◽  
Randomized Controlled

Abstract Background: Several studies have investigated the effects of intrathecal magnesium sulfate as an adjuvant for bupivacaine; however, their conclusions are inconsistent. Therefore, it is necessary to conduct a meta-analysis on this topic.Methods We searched Pubmed, EMBASE (OvidSP) and Cochrane Central Register of Controlled Trials (CENTRAL) for randomized controlled trials (RCTs) comparing the effect of intrathecal bupivacaine combined with magnesium sulfate versus bupivacaine alone in adults using spinal anesthesia.Results Eighteen studies that met our inclusion criteria were included in our analysis. We found that the addition of intrathecal magnesium sulfate to bupivacaine provided a longer duration of analgesia (SMD 0.99; 95% CI [0.45, 1.52], P = 0.0003, I2 = 93%), prolonged the duration of sensory block (MD=106.69; 95% CI, 60.93-152.45; P<0.00001), delayed the onset of sensory block (SMD 1.20; 95% CI [0.65, 1.75], P =<0.0001, I2 = 91%) and motor block (SMD 1.46; 95% CI [0.23, 2.69], P =0.02, I2 = 96%), decreased the requirement for rescue analgesia (SMD -0.81; 95% CI [-1.06, -0.56], P < 0.00001, I2 = 11%). For duration of motor block, and incidence of postoperative adverse events (such as nausea and vomiting, hypotension, bradycardia, pruritus, shivering and neurological deficit), no statistically differences were observed between the 2 groups.Conclusions Our meta-analysis demonstrated that intrathecal magnesium sulfate combined with bupivacaine prolongs the dusration of analgesia, without an impact on the adverse events. However, the quality of evidence was very low when using GRADE to assess it. Given adverse effects before use, more high-quality trials with large samples are required before magnesium sulfate is routinely used as a intrathecal adjunct.

scholarly journals Comparative Efficacy of Pharmacological and Nonpharmacological Interventions for Acne Vulgaris: A Network Meta-Analysis

2020 ◽  
Vol 11 ◽  
Author(s):  
Qingyang Shi ◽  
Lizi Tan ◽  
Zhe Chen ◽  
Long Ge ◽  
Xiaoyan Zhang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Physical Symptoms ◽  
Current Evidence ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Comparative Efficacy ◽  
Inflammatory Lesions ◽  
Randomized Controlled

Acne has several effects on physical symptoms, but the main impacts are on the quality of life, which can be improved by treatment. There are several acne treatments but less evidence comparing their relative efficacy. Thus, we assessed the comparative efficacy of pharmacological and nonpharmacological interventions for acne. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to April 2019, to include randomized controlled trials for acne that compared topical antibiotics (TA), benzoyl peroxide (BPO), topical retinoids (TR), oral antibiotics (OA), lasers, light devices including LED device (LED), photodynamic therapy (PDT), and intense pulsed light, chemical peels (CP), miscellaneous therapies or complementary and alternative medicine (MTCAM), or their combinations. We performed Bayesian network meta-analysis with random effects for all treatments compared with placebo and each other. Mean differences (MDs) of lesions count and risk ratios of adverse events with their 95% credible intervals (CrIs) were calculated, and all interventions were ranked by the Surface Under the Cumulative Ranking (SUCRA) values. Additional frequentist additive network meta-analysis was performed to detect the robustness of results and potential interaction effects. Sensitivity analyses were carried out with different priors, and metaregression was to adjust for nine potential effect modifiers. In the result, seventy-three randomized controlled trials (27,745 patients with mild to moderate acne), comparing 30 grouped intervention categories, were included with low to moderate risk of bias. For adverse effects, OA had more risk in combination treatment with others. For noninflammatory lesions reduction, seventeen interventions had significant differences comparing with placebo and three interventions (TR+BPO: MD = −21.89, 95%CrI [−28.97, −14.76]; TR+BPO+MTCAM: −22.48 [−34.13, −10.70]; TA+BPO+CP: −20.63 [−33.97, −7.13]) were superior to others with 94, 94, and 91% SUCRA values, respectively. For inflammatory lesions reduction, nineteen interventions were significantly better than placebo, and three interventions (TR+BPO: MD = −12.13, 95%CrI [−18.41, −5.80]; TR+BPO+MTCAM: −13.21 [−.39, −3.04]; LED: −11.30 [−18.34, −4.42]) were superior to others (SUCRA: 81, 81, and 77%, respectively). In summary of noninflammatory and inflammatory lesions results, TR+BPO and TA+BPO were the best options compared to others. The frequentist model showed similar results as above. In summary, current evidence supports the suggestion that TR+BPO and TA+BPO are the best options for mild to moderate acne. LED is another option for inflammatory lesions when drug resistance occurs. All the combinations involved with OA showed more risk of adverse events than others. However, the evidence of this study should be cautiously used due to the limitations.

Febuxostat use and risks of CVD events, death from cardiac-cause and all-cause mortality: metaanalysis of randomized controlled trials

2020 ◽  
pp. jrheum.200307
Author(s):  
Hao Deng ◽  
Bao Long Zhang ◽  
Jin Dong Tong ◽  
Xiu Hong Yang ◽  
Hui Min Jin
Keyword(s):  
Web Of Science ◽  
Meta Analysis ◽  
Relevant Literature ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Inclusion Criteria ◽  
Randomized Controlled ◽  
Central Register ◽  
Increased Risk ◽  
All Cause Mortality

Objective To assess whether febuxostat use increases the risk of developing cardiovascular events, death from cardiac-cause and all-cause mortalities. Methods The relevant literature was searched in several databases including the MEDLINE (PubMed, 1 Jan. 1966–29 Feb. 2020), Web of science, EMBASE (1 Jan. 1974–29 Feb. 2020), ClinicalTrials.gov and Cochrane Central Register for Controlled Trials. Manual searches for references cited in the original studies and relevant review articles were also performed. All studies included in this metanalysis were published in English. Results In the end, 20 studies that met our inclusion criteria were included in this meta-analysis. Use of febuxostat was found not to be associated with an increased risk of all-cause mortality (RR = 0.87, 95% CI 0.57–1.32, P =0.507). Also, there was no association between febuxostat use and mortalities arising from cardiovascular diseases (CVD) (RR = 0.84, 95% CI 0.49–1.45, P=0.528). The RR also revealed that febuxostat use was not associated with CVD events (RR = 0.98, 95% CI 0.83–1.16, P =0.827). Furthermore, the likelihood of occurrence of CVD events was found not to be dependent on febuxostat dose (RR = 1.04, 95% CI 0.84–1.30, P =0.723). Conclusion Febuxostat use is not associated with increased risks of all-cause mortality, death from CVD or CVD events. Accordingly, it is a safe drug for the treatment of gout. Systematic review registration: PROSPERO CRD42019131872

scholarly journals Systematic Review of Randomized Clinical Trials of Acupressure Therapy for Primary Dysmenorrhea

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Hui-ru Jiang ◽  
Shuang Ni ◽  
Jin-long Li ◽  
Miao-miao Liu ◽  
Ji Li ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Statistical Analysis ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Primary Dysmenorrhea ◽  
Randomized Controlled ◽  
Central Register

The evidence of acupressure is limited in the management of dysmenorrhea. To evaluate the efficacy of acupressure in the treatment of primary dysmenorrhea based on randomized controlled trials (RCTs), we searched MEDLINE, the Chinese Biomedical Database (CBM), and the Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception until March 2012. Two reviewers independently selected articles and extracted data. Statistical analysis was performed with RevMan 5.1 software. Eight RCTs were identified from the retrieved 224 relevant records. Acupressure improved pain measured with VAS (−1.41 cm 95% CI [−1.61, −1.21]), SF-MPQ at the 3-month followup (WMD −2.33, 95% CI [−4.11, −0.54]) and 6-month followup (WMD −4.67, 95% CI [−7.30, −2.04]), and MDQ at the 3-month followup (WMD −2.31, 95% CI [−3.74, −0.87]) and 6-month followup (WMD −4.67, 95% CI [−7.30, −2.04]). All trials did not report adverse events. These results were limited by the methodological flaws of trials.

scholarly journals Anti–PD-1 and Anti–PD-L1 in Head and Neck Cancer: A Network Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Andrea Botticelli ◽  
Alessio Cirillo ◽  
Lidia Strigari ◽  
Filippo Valentini ◽  
Bruna Cerbelli ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Head And Neck ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Head And Neck Carcinoma ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Risk Of Death ◽  
Randomized Controlled ◽  
Central Register

ObjectiveThe monoclonal antibodies anti-programmed death protein-1 (anti–PD-1) nivolumab and pembrolizumab are the first immune checkpoint inhibitors (ICIs) approved for treatment of recurrent/metastatic head and neck carcinoma R/M HNSCC in first line and in platinum refractory disease. This network meta-analysis aims to investigate the efficacy of anti–PD-1- vs anti–PD-L1-based therapy in R/M HNSCC cancer patients through a systematic review of the literature to provide support for evidence-based treatment decisions. In particular, the effectiveness of ICIs for R/M HNSCC is analyzed according to the different mechanisms of action of the check-points inhibitory drugs in different subgroups of patients.MethodsWe did a systematic literature review and network meta-analysis (NMA) of randomized controlled trials (RCTs) in PubMed, ClinicalTrials.gov, Embase, Medline, the Cochrane Central Register of Controlled Trials, Web of Science. Our search identified a total of five randomized controlled trials: Keynote 040, Keynote 048, Eagle, Condor, Checkmate 141. These trials included 3001 patients. Treatment was sub-categorized into PD-L1–based, PD-1–based, and standard chemotherapy. Treatments were indirectly compared with anti–PD-L1-based therapy.ResultsThe network meta-analysis demonstrated no significant differences in OS between different subgroups except for the metastatic patients in which anti–PD-1-based therapy was associated with significantly less risk of death. Furthermore, anti–PD-1-based therapy appeared to be effective in smoker patients and in human papilloma–negative (HPV) patients. Conversely, anti–PD-L1-based therapy seems to be better efficient in female patients, in locally recurrent setting and in HPV positive patients.ConclusionThis is the first NMA study that aimed to indirectly compare anti–PD-1- and anti–PD-L1-based therapy in HNSCC patients. The results of our NMA could help define a profile of patient responder or resistant to specific classes of immune drugs and can be used to guide/design future studies in the novel scenario of precision immune-oncology.

scholarly journals Right versus left thoracic approach oesophagectomy for oesophageal cancer: a systematic review and meta-analysis protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e030157
Author(s):  
Tianci Chai ◽  
Zhimin Shen ◽  
Sui Chen ◽  
Yuhan Lin ◽  
Zhenyang Zhang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Oesophageal Cancer ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Malignant Tumours ◽  
Central Register ◽  
Registration Number ◽  
Thoracic Approach ◽  
Randomised Controlled

IntroductionOesophageal cancer is one of the most common malignant tumours and has been identified as one of the leading causes of cancer death worldwide. Surgery is considered to be the optimal treatment for patients with resectable oesophageal cancer. Oesophagectomy for oesophageal cancer can significantly extend the survival period of patients and provide a potential opportunity for a cure. However, there is still controversy regarding which thoracic approach (right or left) during oesophagectomy for oesophageal cancer can lead to better surgical outcomes globally. This systematic review and meta-analysis will be performed to determine which thoracic approach during oesophagectomy will achieve longer patient survival and will be more beneficial for patients.Methods and analysisWe will search PubMed, Web of Science, Embase, Cancerlit, the Cochrane Central Register of Controlled Trials and Google Scholar databases for relevant clinical trials published in any language before 1 October 2019. Randomised controlled trials (RCTs), quasi-RCTs, propensity score-matched comparative studies and prospective cohort studies of interest, published or unpublished, that meet the inclusion criteria will be included. Subgroup analysis of the type of operation, tumour pathological stage and ethnicity will be performed.PROSPERO registration numberCRD42019124133.Ethics and disseminationBecause this study will be based on published or unpublished records and studies, there is no need for ethics approval. The results of the study will be published in a peer-reviewed journal.

Placebo and nocebo responses in restless legs syndrome

Neurology ◽  
2017 ◽  
Vol 88 (23) ◽  
pp. 2216-2224 ◽  
Author(s):  
Maria A. Silva ◽  
Gonçalo S. Duarte ◽  
Raquel Camara ◽  
Filipe B. Rodrigues ◽  
Ricardo M. Fernandes ◽  
...  
Keyword(s):  
Adverse Events ◽  
Restless Legs Syndrome ◽  
Meta Analysis ◽  
Placebo Response ◽  
Controlled Trials ◽  
Pool Data ◽  
Double Blind ◽  
Restless Legs ◽  
Statistical Heterogeneity ◽  
Registration Number

Objective:To estimate the placebo and nocebo responses in restless legs syndrome (RLS) and explore their determinants.Methods:Databases were searched up to October 2015. Randomized, double-blind, placebo-controlled trials of patients with RLS were included if quantitative data were extractable in the placebo arm. Placebo response was defined as the within-group change from baseline, using any scale measuring RLS severity or disability. Nocebo response was defined as the proportion of patients experiencing adverse events in the placebo arm. Random-effects meta-analysis was used to pool data. Statistical heterogeneity was assessed with I2 statistic. Several predetermined subgroup and sensitivity analysis were performed. PROSPERO registration number is CRD42015027992.Results:We included 85 randomized controlled trials (5,046 participants). Pooled placebo response effect size was −1.41 (95% confidence interval [CI] −1.56 to −1.25, 64 trials, I2 = 88.1%), corresponding to −6.58 points in the International RLS Study Group Scale (IRLS). Pooled nocebo response was 45.36% (95% CI 40.47%–50.29%, 72 trials; I2 = 89.8%). The placebo and nocebo responses were greater in trials with longer duration, evaluating pharmacologic interventions and idiopathic RLS, and in industry-funded and unpublished studies. The placebo response was considerably smaller in objective as compared to subjective outcomes. In addition, the nocebo response increases proportionally with the placebo response, and has the same predictors.Conclusions:The magnitude of the placebo response in RLS is above the threshold of minimal clinical important difference, and the frequency of adverse events is also considerable. These results are relevant to inform the design and interpretation of future clinical trials.

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